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VUEs.txt
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hugoGeneSymbol genomicLocationDescription defaultEffect comment context variant genomicLocation transcriptId hgvsc vepPredictedProteinEffect vepPredictedVariantClassification revisedProteinEffect revisedVariantClassification revisedStandardVariantClassification otherVariation confirmed mutationOrigin variantNote pubmedId referenceText mskimpact_germlineVariantsCount mskimpact_somaticVariantsCount mskimpact_unknownVariantsCount mskimpact_totalPatientCount mskimpact_genePatientCount tcga_germlineVariantsCount tcga_somaticVariantsCount tcga_unknownVariantsCount tcga_totalPatientCount tcga_genePatientCount genie_germlineVariantsCount genie_somaticVariantsCount genie_unknownVariantsCount genie_totalPatientCount genie_genePatientCount mskimpact_nonsignedout_germlineVariantsCount mskimpact_nonsignedout_somaticVariantsCount mskimpact_nonsignedout_unknownVariantsCount mskimpact_nonsignedout_totalPatientCount mskimpact_nonsignedout_genePatientCount
KIT Deletions flanking intron 10 - exon 11 boundary (e.g. 4:55593576_55593606del) splice Changes splice donor site, cause inframe deletion in exon 11 Actionable in GIST 4:g.55593576_55593606del 4,55593576,55593606,CCACAGAAACCCATGTATGAAGTACAGTGGA,- ENST00000288135 ENST00000288135.5:c.1648-6_1672del p.X550_splice Splice_Site p.K550_K558del Splice_Exon_Shortening_In_Frame In_Frame_Del TRUE 15507676 Corless et al., 2004 0 3 0 70067 466 0 0 0 10953 0 0 3 0 60702 428 0 0 0 87119 44
KIT Deletions flanking intron 10 - exon 11 boundary (e.g. 4:55593576_55593606del) splice Changes splice donor site, cause inframe deletion in exon 11 Actionable in GIST 4:g.55593580_55593606del 4,55593580,55593606,AGAAACCCATGTATGAAGTACAGTGGA,- ENST00000288135 ENST00000288135.5:c.1648_1674del p.X550_splice Splice_Site p.K550_K558del Splice_Exon_Shortening_In_Frame In_Frame_Del TRUE 15507676 Corless et al., 2004 0 5 0 70067 466 0 0 0 10953 0 0 5 0 60702 428 0 0 0 87119 44
KIT Deletions flanking intron 10 - exon 11 boundary (e.g. 4:55593576_55593606del) splice Changes splice donor site, cause inframe deletion in exon 11 Actionable in GIST 4:g.55593578_55593606del 4,55593578,55593606,ACAGAAACCCATGTATGAAGTACAGTGGA,- ENST00000288135 ENST00000288135.5:c.1648-3_1673del p.X550_splice Splice_Site p.K550_K558del Splice_Exon_Shortening_In_Frame In_Frame_Del TRUE 15507676 Corless et al., 2004 0 3 0 70067 466 0 0 0 10953 0 0 3 0 60702 428 0 0 0 87119 44
APC 5:g.112151184A>G splice Introduces splice acceptor site causing a frameshift Recurrent alteration in CRC 5:g.112151184A>G 5,112151184,112151184,A,G ENST00000257430 ENST00000257430.4:c.835-8A>G p.*279* Splice_Region p.G279Ffs*10 Splice_Exon_Extension_Frame_Shift Frame_Shift_Ins TRUE 29316426 Yaeger et al., 2018 0 0 0 70067 5978 0 0 0 10953 8 0 0 0 60702 5140 0 321 0 87119 682
BAP1 3:g.52439306A>G synonymous Leads to exon 11 skipping Recurrent and prognostic in kidney cancer 3:g.52439306A>G 3,52439306,52439306,A,G ENST00000460680 ENST00000460680.1:c.936T>C p.G312= Silent p.D311Gfs*23 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE 33681728 Niersch et al., 2021 0 0 0 70067 848 0 0 0 10953 4 0 0 0 60702 758 0 0 0 87119 156
KRAS 12:g.25380277G>T missense Introduces a splice donor site if Q61K is not co-occurring with G60G Recurrent in many cancer types 12:g.25380277G>T 12,25380277,25380277,G,T ENST00000256078 ENST00000256078.4:c.181C>A p.Q61K Missense_Mutation p.X61 Splice_Exon_Shortening_Frame_Shift Frame_Shift_Del FALSE 35236983 Kobayashi et al., 2022 0 7 0 70067 2082 0 0 7 10953 0 0 7 0 60702 2148 0 0 0 87119 423
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266086_41266304del 3,41266086,41266304,AGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAA,- ENST00000349496 ENST00000349496.5:c.86_241+63del p.X29_splice Splice_Site p.Q28_D81del Splice_Exon_Shortening_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 1 0 70067 751 0 0 0 10953 0 0 1 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266012_41266312del 3,41266012,41266312,TATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTG,- ENST00000349496 ENST00000349496.5:c.14-1_241+72del p.X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 1 0 70067 751 0 0 0 10953 0 0 1 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266038_41266264del 3,41266038,41266264,TGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCAT,- ENST00000349496 ENST00000349496.5:c.37_241+22del p.X13_splice Splice_Site p.M12_D81del Splice_Exon_Shortening_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 1 0 70067 751 0 0 0 10953 0 0 1 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265709_41266219del 3,41265709,41266219,TCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAG,- ENST00000349496 ENST00000349496.5:c.13+141_220del p.X5_splice Splice_Site p.A5_Q72del Splice_Exon_Shortening_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 1 0 70067 751 0 0 0 10953 0 0 1 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266090_41266253del 3,41266090,41266253,TTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTA,- ENST00000349496 ENST00000349496.5:c.90_241+12del p.X30_splice Splice_Site p.S29_D81del Splice_Exon_Shortening_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 1 0 70067 751 0 0 0 10953 0 0 1 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265579_41266277del 3,41265579,41266277,GTCATTAAATCTTTAGTTACTGAATTGGGGCTCTGCTTCGTTGCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAA,- ENST00000349496 ENST00000349496.5:c.13+11_241+37del p.X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 1 0 70067 751 0 0 0 10953 0 0 1 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265722_41266253del 3,41265722,41266253,TTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTA,- ENST00000349496 ENST00000349496.5:c.13+152_241+11del p.X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 1 0 70067 751 0 0 0 10953 0 0 1 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266029_41266287del 3,41266029,41266287,AGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGC,- ENST00000349496 ENST00000349496.5:c.30_241+47del p.X10_splice Splice_Site p.E9_D81del Splice_Exon_Shortening_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 1 0 70067 751 0 0 0 10953 0 0 1 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266028_41266420del 3,41266028,41266420,GAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGT,- ENST00000349496 ENST00000349496.5:c.29_242-21del p.X10_splice Splice_Site p.E9_D81del Splice_Exon_Shortening_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 1 0 70067 751 0 0 0 10953 0 0 1 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266016_41266403del 3,41266016,41266403,GCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAAT,- ENST00000349496 ENST00000349496.5:c.18_242-37del p.X6_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 1 0 70067 751 0 0 0 10953 0 0 1 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265975_41266211del 3,41265975,41266211,CATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGAT,- ENST00000349496 ENST00000349496.5:c.14-42_208del p.X5_splice Splice_Site p.A5_G69del Splice_Exon_Shortening_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 1 0 70067 751 0 0 0 10953 0 0 1 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265908_41266236del 3,41265908,41266236,TTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACA,- ENST00000349496 ENST00000349496.5:c.14-109_233del p.X5_splice Splice_Site p.A5_Q79del Splice_Exon_Shortening_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 1 0 70067 751 0 0 0 10953 0 0 1 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266013_41266355del 3,41266013,41266355,ATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTA,- ENST00000349496 ENST00000349496.5:c.15_242-85del p.X5_splice Splice_Site p.A5_D81del Splice_Exon_Skip_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 1 0 70067 751 0 0 0 10953 0 0 1 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265897_41266218del 3,41265897,41266218,GTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCA,- ENST00000349496 ENST00000349496.5:c.14-117_218del p.X5_splice Splice_Site p.A5_Q72del Splice_Exon_Shortening_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 1 0 70067 751 0 0 0 10953 0 0 1 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41266002_41266029del 3,41266002,41266029,GTTTCGTATTTATAGCTGATTTGATGGA,- ENST00000349496 ENST00000349496.5:c.14-12_29del p.X5_splice Splice_Site p.A5_E9del Splice_Exon_Shortening_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 1 0 70067 751 0 0 0 10953 0 0 1 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265562_41266260del 3,41265562,41266260,GGCTACTCAAGGTTTGTGTCATTAAATCTTTAGTTACTGAATTGGGGCTCTGCTTCGTTGCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTT,- ENST00000349496 ENST00000349496.5:c.3_241+16del p.X1_splice Splice_Site p.A2_D81del Splice_Exon_Skip_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 0 0 70067 751 0 0 0 10953 0 0 0 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265568_41266266del 3,41265568,41266266,TCAAGGTTTGTGTCATTAAATCTTTAGTTACTGAATTGGGGCTCTGCTTCGTTGCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTG,- ENST00000349496 ENST00000349496.5:c.9_241+22del p.X3_splice Splice_Site p.Q4_D81del Splice_Exon_Skip_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 0 0 70067 751 0 0 0 10953 0 0 0 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265571_41266206del 3,41265571,41266206,AGGTTTGTGTCATTAAATCTTTAGTTACTGAATTGGGGCTCTGCTTCGTTGCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACA,- ENST00000349496 ENST00000349496.5:c.12_203del p.X4_splice Splice_Site p.A5_Q68del Splice_Exon_Skip_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 0 0 70067 751 0 0 0 10953 0 0 0 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265648_41266493del 3,41265648,41266493,CCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGC,- ENST00000349496 ENST00000349496.5:c.13+76_290del p.X5_splice Splice_Site p.A5_A97del Splice_Exon_Skip_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 0 0 70067 751 0 0 0 10953 0 0 0 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265674_41266212del 3,41265674,41266212,TTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATT,- ENST00000349496 ENST00000349496.5:c.13+104_211del p.X5_splice Splice_Site p.A5_F70del Splice_Exon_Shortening_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 0 0 70067 751 0 0 0 10953 0 0 0 0 60702 664 0 0 0 87119 51
CTNNB1 Deletions flanking exon 2-3 (e.g. 3:41265579_41266277del) splice, intron Complete exon 3 skip or inframe deletion in exon 3 Recurrent alteration in CRC 3:g.41265990_41266204del 3,41265990,41266204,AATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAA,- ENST00000349496 ENST00000349496.5:c.14-27_201del p.X5_splice Splice_Site p.A5_Q68del Splice_Exon_Shortening_In_Frame In_Frame_Del TRUE 29316426 Yaeger et al., 2018 0 0 0 70067 751 0 0 0 10953 0 0 0 0 60702 664 0 0 0 87119 51
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116411926_116412083del 7,116411926,116412083,TACGATGCAAGAGTACACACTCCTCATTTGGATAGGCTTGTAAGTGCCCGAAGTGTAAGCCCAACTACAGAAATGGTTTCAAATGAATCTGTAGACTACCGAGCTACTTTTCCAGAAGGTATATTTCAGTTTATTGTTCTGAGAAATACCTATACATA,- ENST00000397752 ENST00000397752.3:c.2914_3028+43del p.X972_splice Splice_Site p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 27343443 Schrock et al., 2014 0 1 0 70067 141 0 0 0 10953 0 0 1 0 60702 122 0 0 0 87119 42
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116411770_116412349del 7,116411770,116412349,AGATTGTCGTCGATTCTTGTGTGCTGTCTTATATGTAGTCCATAAAACCCATGAGTTCTGGGCACTGGGTCAAAGTCTCCTGGGGCCCATGATAGCCGTCTTTAACAAGCTCTTTCTTTCTCTCTGTTTTAAGATCTGGGCAGTGAATTAGTTCGCTACGATGCAAGAGTACACACTCCTCATTTGGATAGGCTTGTAAGTGCCCGAAGTGTAAGCCCAACTACAGAAATGGTTTCAAATGAATCTGTAGACTACCGAGCTACTTTTCCAGAAGGTATATTTCAGTTTATTGTTCTGAGAAATACCTATACATATACCTCAGTGGGTTGTGACATTGTTGTTTATTTTTGGTTTTGCATTTATATTTTTATAAAAACCTAAAGGAAGTATTTACCTCTGCCAAGTAAGTATTTGACACAAAATTACATGGCTCTTAATTTTAAAAGAACCCATGTATATATTACATTATGATTTTAGAGTCCATAAGCTCTCATTTCACAAAAAGGTTAATTTGAGCAAAAGTAATTTGTTTATCATCTAAGTGCAATAGTAAGAAATTGCGAAGCTCTCTTTTACAATC,- ENST00000397752 ENST00000397752.3:c.2887+62_3028+306del p.X963_splice Splice_Site p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 27343443 Schrock et al., 2014 0 1 0 70067 141 0 0 0 10953 0 0 0 0 60702 122 0 0 0 87119 42
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116411818_116412557del 7,116411818,116412557,CCATGAGTTCTGGGCACTGGGTCAAAGTCTCCTGGGGCCCATGATAGCCGTCTTTAACAAGCTCTTTCTTTCTCTCTGTTTTAAGATCTGGGCAGTGAATTAGTTCGCTACGATGCAAGAGTACACACTCCTCATTTGGATAGGCTTGTAAGTGCCCGAAGTGTAAGCCCAACTACAGAAATGGTTTCAAATGAATCTGTAGACTACCGAGCTACTTTTCCAGAAGGTATATTTCAGTTTATTGTTCTGAGAAATACCTATACATATACCTCAGTGGGTTGTGACATTGTTGTTTATTTTTGGTTTTGCATTTATATTTTTATAAAAACCTAAAGGAAGTATTTACCTCTGCCAAGTAAGTATTTGACACAAAATTACATGGCTCTTAATTTTAAAAGAACCCATGTATATATTACATTATGATTTTAGAGTCCATAAGCTCTCATTTCACAAAAAGGTTAATTTGAGCAAAAGTAATTTGTTTATCATCTAAGTGCAATAGTAAGAAATTGCGAAGCTCTCTTTTACAATCCAGGAAGAGTTAAGTTACAAAATATACTTATTTAAATGTAAGTTGGAACTGCTACATTTTTTACCTGTTGAAGCCCAAACATTGAAATTATACTGTTAGTAATTCTTCGAAGTGTTTTCAATGAACTGTTAGTACACAGCCTTTTTCCCACCATATTCTAGGACTTGAATGTATTTTGAGACTTAGCCAAGGAAAACCTTCAATTATG,- ENST00000397752 ENST00000397752.3:c.2888-79_3028+520del p.X963_splice Splice_Site p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 27343443 Schrock et al., 2014 0 1 0 70067 141 0 0 0 10953 0 0 1 0 60702 122 0 0 0 87119 42
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116411874_116411897del 7,116411874,116411897,ACAAGCTCTTTCTTTCTCTCTGTT,- ENST00000397752 ENST00000397752.3:c.2888-29_2888-6del p.X963_splice Splice_Region p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Confirmed by MSK Clinical Bioinformatics Team (Unpublished) 0 0 0 70067 141 0 0 0 10953 0 0 0 0 60702 122 0 0 0 87119 42
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116411881_116411897del 7,116411881,116411897,CTTTCTTTCTCTCTGTT,- ENST00000397752 ENST00000397752.3:c.2888-22_2888-6del p.X963_splice Splice_Region p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Confirmed by MSK Clinical Bioinformatics Team (Unpublished) 0 0 0 70067 141 0 0 0 10953 0 0 0 0 60702 122 0 0 0 87119 42
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116411881_116411937del 7,116411881,116411937,CTTTCTTTCTCTCTGTTTTAAGATCTGGGCAGTGAATTAGTTCGCTACGATGCAAGA,- ENST00000397752 ENST00000397752.3:c.2888-22_2922del p.X963_splice Splice_Site p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Confirmed by MSK Clinical Bioinformatics Team (Unpublished) 0 0 0 70067 141 0 0 0 10953 0 0 0 0 60702 122 0 0 0 87119 42
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116411860_116411888del 7,116411860,116411888,GATAGCCGTCTTTAACAAGCTCTTTCTTT,- ENST00000397752 ENST00000397752.3:c.2888-43_2888-15del p.*963* Intron p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Confirmed by MSK Clinical Bioinformatics Team (Unpublished) 0 0 0 70067 141 0 0 0 10953 0 0 0 0 60702 122 0 0 0 87119 42
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116411879_116411896del 7,116411879,116411896,CTCTTTCTTTCTCTCTGT,- ENST00000397752 ENST00000397752.3:c.2888-24_2888-7del p.X963_splice Splice_Region p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Confirmed by MSK Clinical Bioinformatics Team (Unpublished) 0 0 0 70067 141 0 0 0 10953 0 0 0 0 60702 122 0 0 0 87119 42
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116412046A>G 7,116412046,116412046,A,G ENST00000397752 ENST00000397752.3:c.3028+3A>G p.X1010_splice Splice_Region p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Confirmed by MSK Clinical Bioinformatics Team (Unpublished) 0 16 0 70067 141 0 0 0 10953 0 0 14 0 60702 122 0 3 1 87119 42
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116411879_116411897del 7,116411879,116411897,CTCTTTCTTTCTCTCTGTT,- ENST00000397752 ENST00000397752.3:c.2888-24_2888-6del p.X963_splice Splice_Region p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Confirmed by MSK Clinical Bioinformatics Team (Unpublished) 0 0 0 70067 141 0 0 0 10953 0 0 0 0 60702 122 0 0 0 87119 42
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116411887_116411906del 7,116411887,116411906,TTCTCTCTGTTTTAAGATCT,- ENST00000397752 ENST00000397752.3:c.2888-16_2891del p.X963_splice Splice_Site p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Confirmed by MSK Clinical Bioinformatics Team (Unpublished) 0 0 0 70067 141 0 0 0 10953 0 0 0 0 60702 122 0 0 0 87119 42
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116412043G>A 7,116412043,116412043,G,A ENST00000397752 ENST00000397752.3:c.3028G>A p.D1010N Missense_Mutation p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Confirmed by MSK Clinical Bioinformatics Team (Unpublished) 0 38 1 70067 141 0 0 0 10953 0 0 34 1 60702 122 0 0 0 87119 42
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116411885_116411897del 7,116411885,116411897,CTTTCTCTCTGTT,- ENST00000397752 ENST00000397752.3:c.2888-18_2888-6del p.X963_splice Splice_Region p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Confirmed by MSK Clinical Bioinformatics Team (Unpublished) 0 0 0 70067 141 0 0 0 10953 0 0 0 0 60702 122 0 0 0 87119 42
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116412041_116412044del 7,116412041,116412044,AAGG,- ENST00000397752 ENST00000397752.3:c.3026_3028+1del p.X1009_splice Splice_Site p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Confirmed by MSK Clinical Bioinformatics Team (Unpublished) 0 0 0 70067 141 0 0 0 10953 0 0 0 0 60702 122 0 0 0 87119 42
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116411881_116411895del 7,116411881,116411895,CTTTCTTTCTCTCTG,- ENST00000397752 ENST00000397752.3:c.2888-22_2888-8del p.X963_splice Splice_Region p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Confirmed by MSK Clinical Bioinformatics Team (Unpublished) 0 0 0 70067 141 0 0 0 10953 0 0 0 0 60702 122 0 0 0 87119 42
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116411867_116411882del 7,116411867,116411882,GTCTTTAACAAGCTCT,- ENST00000397752 ENST00000397752.3:c.2888-36_2888-21del p.*963* Intron p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Confirmed by MSK Clinical Bioinformatics Team (Unpublished) 0 0 0 70067 141 0 0 0 10953 0 0 0 0 60702 122 0 0 0 87119 42
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116412044G>A 7,116412044,116412044,G,A ENST00000397752 ENST00000397752.3:c.3028+1G>A p.X1010_splice Splice_Site p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Confirmed by MSK Clinical Bioinformatics Team (Unpublished) 0 19 0 70067 141 0 0 1 10953 0 0 14 0 60702 122 0 0 0 87119 42
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116411876_116411896del 7,116411876,116411896,AAGCTCTTTCTTTCTCTCTGT,- ENST00000397752 ENST00000397752.3:c.2888-27_2888-7del p.X963_splice Splice_Region p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Confirmed by MSK Clinical Bioinformatics Team (Unpublished) 0 0 0 70067 141 0 0 0 10953 0 0 0 0 60702 122 0 0 0 87119 42
MET Indels and substitutions flanking exon 14 (e.g. 7:116411926_116412083del) splice Skipping of exon 14 Actionable in NSCLC 7:g.116411867_116411890del 7,116411867,116411890,GTCTTTAACAAGCTCTTTCTTTCT,- ENST00000397752 ENST00000397752.3:c.2888-36_2888-13del p.*963* Intron p.D963_D1010del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 0 Confirmed by MSK Clinical Bioinformatics Team (Unpublished) 0 0 0 70067 141 0 0 0 10953 0 0 0 0 60702 122 0 0 0 87119 42
PIK3R1 Indels and substitutions flanking exon 11 (e.g. 5:67589663G>A) splice Skipping of exon 11 Recurrent in breast and uterine cancer 5:g.67589663G>C 5,67589663,67589663,G,C ENST00000521381 ENST00000521381.1:c.1425+1G>C p.X475_splice Splice_Site p.D434_E476del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 25488983 Lucas et al., 2014 0 2 0 70067 99 0 0 0 10953 0 0 2 0 60702 86 0 0 0 87119 16
FLT3 Indels around tyrosine kinase (e.g. 13:28608214_28608215insTT...) splice Internal Tandem Duplication Recurrent alteration in AML 13:g.28608217_28608218insCCAAACTCTAAATTTTCTCTTGGAAACTCCCATTTGAGATCATATTCATATTCTCTG 13,28608217,28608218,-,CCAAACTCTAAATTTTCTCTTGGAAACTCCCATTTGAGATCATATTCATATTCTCTG ENST00000241453 ENST00000241453.7:c.1782_1837+1dup p.X594_splice Splice_Site p.E598_F612dup Splice_Exon_Extension_In_Frame In_Frame_Ins FALSE 31285539 Zhang et al., 2020 0 0 0 70067 89 0 0 0 10953 1 0 0 0 60702 83 0 0 0 87119 74
ATM Mutations at canonical splice sites predicted to alter splicing missense, splice Splice leads to exon skip, frameshift and inframe deletion In ataxia telangiectasia and familial prostate cancer, increase the risk of breast and pancreatic cancer 11:g.108115753G>A 11,108115753,108115753,G,A ENST00000278616 ENST00000278616.4:c.901G>A p.G301S Missense_Mutation p.C222Qfs*2 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE germline 31843900 Casadei et al., 2019 0 0 0 70067 1512 0 0 0 10953 6 0 0 0 60702 1288 0 0 0 87119 797
ATM Mutations at canonical splice sites predicted to alter splicing missense, splice Splice leads to exon skip, frameshift and inframe deletion In ataxia telangiectasia and familial prostate cancer, increase the risk of breast and pancreatic cancer 11:g.108127067G>A 11,108127067,108127067,G,A ENST00000278616 ENST00000278616.4:c.2250G>A p.X750_splice Splice_Region p.I709_K750del Splice_Exon_Skip_In_Frame In_Frame_Del TRUE germline This heterozygous germline variant ATM c.2250G>A variant does not change the encoded amino acid of the ATM protein (p.Lys750=), however, it falls at the last base pair of exon 14 of ATM. This variant has been identified in <0.01% of Non-Finnish European chromosomes in the genome Aggregation Database (http://gnomad.broadinstitute.org). It has been reported in combination with another pathogenic variant in individuals and families with Ataxia-telangiectasia (PMID: 9463314, 10980530, 9887333, 10330348, 19691550). It has also been reported in the heterozygous state in a BRCA1/2 negative individual undergoing multigene panel testing (PMID:26270727). An experimental study showed that this variant affects splicing and leads to exon skipping of exon 14 (PMID: 9887333). This variant is classified as pathogenic. ATM truncating mutations may increase the risk of breast cancer and pancreatic cancer (PMID: 21787400; PMID: 22585167) and have been reported in families with familial prostate cancer (PMID: 24556621.). Ataxia-telangiectasia is an autosomal recessive condition characterized by progressive cerebellar ataxia, telangiectasias, immunodeficiency, and increased cancer risks and is caused by two mutations (one affecting each allele) in the ATM gene. If an ATM mutation carrier's partner is heterozygous for a pathogenic ATM mutation, there is a 25% risk that each child would be affected by ataxia-telangiectasia. 9887333;31843900 Sandoval et al., 1999;Casadei et al., 2019 0 0 0 70067 1512 0 0 0 10953 6 0 0 0 60702 1288 0 3 0 87119 797
ATM Mutations at canonical splice sites predicted to alter splicing missense, splice Splice leads to exon skip, frameshift and inframe deletion In ataxia telangiectasia and familial prostate cancer, increase the risk of breast and pancreatic cancer 11:g.108138071T>C 11,108138071,108138071,T,C ENST00000278616 ENST00000278616.4:c.2638+2T>C p.X880_splice Splice_Site p.A823Vfs*5 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE germline 31843900 Casadei et al., 2019 0 1 0 70067 1512 0 0 0 10953 6 0 0 0 60702 1288 0 0 0 87119 797
ATM Mutations at canonical splice sites predicted to alter splicing missense, splice Splice leads to exon skip, frameshift and inframe deletion In ataxia telangiectasia and familial prostate cancer, increase the risk of breast and pancreatic cancer 11:g.108175400A>C 11,108175400,108175400,A,C ENST00000278616 ENST00000278616.4:c.5497-2A>C p.X1833_splice Splice_Site p.V1833Ifs*63 Splice_Exon_Shortening_Frame_Shift Frame_Shift_Del FALSE germline 31843900 Casadei et al., 2019 0 0 0 70067 1512 0 0 0 10953 6 0 0 0 60702 1288 0 0 0 87119 797
ATM Mutations at canonical splice sites predicted to alter splicing missense, splice Splice leads to exon skip, frameshift and inframe deletion In ataxia telangiectasia and familial prostate cancer, increase the risk of breast and pancreatic cancer 11:g.108198370A>C 11,108198370,108198370,A,C ENST00000278616 ENST00000278616.4:c.6976-2A>C p.X2326_splice Splice_Site p.N2326_K2363del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE germline 31843900 Casadei et al., 2019 0 0 0 70067 1512 0 0 0 10953 6 0 0 0 60702 1288 0 0 0 87119 797
ATM Mutations at canonical splice sites predicted to alter splicing missense, splice Splice leads to exon skip, frameshift and inframe deletion In ataxia telangiectasia and familial prostate cancer, increase the risk of breast and pancreatic cancer 11:g.108198484_108198522del 11,108198484,108198522,AGGTAAGATTTTTGGAGCAACCCTTAAGATAGTTACTTA,- ENST00000278616 ENST00000278616.4:c.7088_7089+37del p.X2363_splice Splice_Site p.N2326_K2363del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE germline 31843900 Casadei et al., 2019 0 0 0 70067 1512 0 0 0 10953 6 0 0 0 60702 1288 0 0 0 87119 797
ATM Mutations at canonical splice sites predicted to alter splicing missense, splice Splice leads to exon skip, frameshift and inframe deletion In ataxia telangiectasia and familial prostate cancer, increase the risk of breast and pancreatic cancer 11:g.108214099_108214103del 11,108214099,108214103,GTGAG,- ENST00000278616 ENST00000278616.4:c.8418+1_8418+5del p.X2806_splice Splice_Site p.V2757_M2806del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE germline 31843900 Casadei et al., 2019 0 0 0 70067 1512 0 0 0 10953 6 0 0 0 60702 1288 0 0 0 87119 797
ATM Mutations at canonical splice sites predicted to alter splicing missense, splice Splice leads to exon skip, frameshift and inframe deletion In ataxia telangiectasia and familial prostate cancer, increase the risk of breast and pancreatic cancer 11:g.108236051G>A 11,108236051,108236051,G,A ENST00000278616 ENST00000278616.4:c.8988-1G>A p.X2996_splice Splice_Site p.S2996Rfs*5 Splice_Exon_Shortening_Frame_Shift Frame_Shift_Del FALSE germline 31843900 Casadei et al., 2019 0 0 0 70067 1512 0 0 0 10953 6 0 0 0 60702 1288 0 0 0 87119 797
ATM Mutations at canonical splice sites predicted to alter splicing missense, splice Splice leads to exon skip, frameshift and inframe deletion In ataxia telangiectasia and familial prostate cancer, increase the risk of breast and pancreatic cancer 11:g.108202764G>A 11,108202764,108202764,G,A ENST00000278616 ENST00000278616.4:c.7788G>A p.X2596_splice Splice_Region p.L2544_E2596del Splice_Exon_Skip_In_Frame In_Frame_Del TRUE germline This heterozygous ATM c.7788G>A p.Glu2596Glu variant is a synonymous variant that occurs at the last nucleotide of exon 52 and does not alter the amino acid at this position. It has been identified in 0.002% of Non-Finnish European chromosomes by the Exome Aggregation Consortium (ExAC: http://exac.broadinstitute.org; dbSNP). This variant has been reported in two homozygous and one compound heterozygous individuals with ataxia-telangiectasia (PMID: 9792409 and 26693373). It has been demonstrated to cause altered splicing, leading to deletion of 53 amino acids in exon 52 (PMID: 9792409). This region includes part of the FAT domain, which has been suggested to be important for proper activity of the protein (PMID: 23532176, 25460276, 10782091, 27229179). In summary, based on the previous reports of this variant in individuals with ataxia-telangiectasia and its impact on the protein, this variant meets our criteria to be classified as pathogenic. ATM truncating mutations may increase the risk of breast cancer and pancreatic cancer (PMID: 21787400; PMID: 22585167) and have been reported in families with familial prostate cancer (PMID: 24556621.) Ataxia-telangiectasia is an autosomal recessive condition characterized by progressive cerebellar ataxia, telangiectasias, immunodeficiency, and increased cancer risks and is caused by two mutations (one affecting each allele) in the ATM gene. If an ATM mutation carrier's partner is heterozygous for a pathogenic ATM mutation, there is a 25% risk that each child would be affected by ataxia-telangiectasia. 9792409 Broeks et al., 1998 0 0 0 70067 1512 0 0 0 10953 6 0 0 0 60702 1288 0 0 0 87119 797
ATM Mutations at canonical splice sites predicted to alter splicing missense, splice Splice leads to exon skip, frameshift and inframe deletion In ataxia telangiectasia and familial prostate cancer, increase the risk of breast and pancreatic cancer 11:g.108151895G>A 11,108151895,108151895,G,A ENST00000278616 ENST00000278616.4:c.3576G>A p.X1192_splice Splice_Region p.S1135_K1192 Splice_Exon_Skip_In_Frame In_Frame_Del TRUE germline This heterozygous ATM c.3576G>A variant is a synonymous alteration that does not change a Lysine to another amino acid at codon 1192 (p.Lys1192=). This variant occurs in the last nucleotide of an exon and leads to aberrant splicing leading to exon skipping according to in-vitro RNA studies (PMID: 9887333, 16941484, 21965147). This variant has been identified in 4/113572 of Non-Finnish European chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/;), and has been reported in multiple individuals with ataxia telangiectasia in heterozygous (in-trans with another pathogenic ATM variant) or homozygous states (PMID: 30819809, 8845835, 9443866, 9792409, 9887333, 10330348, 12552559, 16941484, 17124347). Furthermore, this variant has been detected in patients with breast, thyroid or ampullary cancers (PMID: 27599564, 30620386, 31300551). In summary, based on the previous reports of this variant in individuals with ATM associated disease and in-vitro functional studies, this variant is classified as pathogenic. ATM truncating mutations may increase the risk of breast cancer and pancreatic cancer (PMID: 21787400; PMID: 22585167) and have been reported in families with familial prostate cancer (PMID: 24556621.) Ataxia-telangiectasia is an autosomal recessive condition characterized by progressive cerebellar ataxia, telangiectasias, immunodeficiency, and increased cancer risks and is caused by two mutations (one affecting each allele) in the ATM gene. If an ATM mutation carrier's partner is heterozygous for a pathogenic ATM mutation, there is a 25% risk that each child would be affected by ataxia-telangiectasia. 9887333;16941484;21965147 Sandoval et al., 1999;Cavalieri et al., 2006;Demuth et al., 2011 0 0 0 70067 1512 0 0 0 10953 6 0 0 0 60702 1288 0 1 0 87119 797
BRCA1 Mutations at canonical splice sites predicted to alter splicing missense, splice, intron Splice leads to frameshift 17:g.41197820C>T 17,41197820,41197820,C,T ENST00000357654 ENST00000357654.3:c.5468-1G>A p.X1823_splice Splice_Site p.A1844Dfs*2 Splice_Exon_Shortening_Frame_Shift Frame_Shift_Del FALSE germline 31843900 Casadei et al., 2019 0 0 0 70067 407 0 0 0 10953 0 0 0 0 60702 351 0 0 0 87119 330
BRCA1 Mutations at canonical splice sites predicted to alter splicing missense, splice, intron Splice leads to frameshift 17:g.41228505C>A 17,41228505,41228505,C,A ENST00000357654 ENST00000357654.3:c.4484G>T p.R1495M Missense_Mutation p.A1453Gfs*9 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE germline 31843900 Casadei et al., 2019 0 2 0 70067 407 0 0 0 10953 0 0 1 0 60702 351 0 0 0 87119 330
BRCA1 Mutations at canonical splice sites predicted to alter splicing missense, splice, intron Splice leads to deletion of 22 bp at the end of exon 5 17:g.41258474T>C 17,41258474,41258474,T,C ENST00000357654 ENST00000357654:c.211A>G p.R71G Missense_Mutation p.C64* Splice_Exon_Shortening_Frame_Shift Frame_Shift_Del FALSE The BRCA1 c.211A>G variant changes an arginine to glycine at codon 71 (p.R71G). This variant has been identified in 1/249744 chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/), and has been reported as a founder mutation in the Spanish population shown to segregate with breast and ovarian cancer in multiple families (PMID: 11385711, 23683081, 27081505, 12014998, 20215541). According to RT-PCR analysis, this variants leads to an aberrantly spliced mRNA creating a premature stop codon (p.Cys64*) (PMID: 11385711, 19123044, 20215541, 21735045). Heterozygous truncating variants in BRCA1 are known to be pathogenic. Note: this variant is also known as 330A>G in the literature. The sequence analysis indicated that 22 base pairs of exon 4 were deleted, creating with the first bases of exon 5, a termination codon at position 64 21735045;11385711 Menéndez et al., 2012;Vega et al., 2001
BRCA1 Mutations at canonical splice sites predicted to alter splicing missense, splice, intron Splice leads to deletion of 22 bp at the end of exon 5 17:g.41258472C>T 17,41258472,41258472,C,T ENST00000357654 ENST00000357654:c.212+1G>A p.X71_splice Splice_Site p.C64* Splice_Exon_Shortening_Frame_Shift Frame_Shift_Del FALSE Deletion of 22 bp at the end of exon 4 21735045 Menéndez et al., 2012
BRCA1 Mutations predicted to alter splicing missense, splice, intron Splice leads to insertion of 11 bp of intro 4 at the beginning of exon 5 17:g.41256985T>C 17,41256985,41256985,T,C ENST00000357654 ENST00000357654:c.213-12A>G p.*71* Intron p.R71Sfs*20 Splice_Exon_Extension_Frame_Shift Frame_Shift_Ins FALSE Insertion of 11 bp of intro 4 at the beginning of exon 5 21735045 Menéndez et al., 2012
BRCA1 Mutations predicted to alter splicing missense, splice, intron Splice leads to skipping of exon 12 17:g.41234420C>A 7,116412044,116412044,G,A ENST00000357654 ENST00000357654:c.4357+1G>T p.X1453_splice Splice_Site p.R1397Yfs*2 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del Deletion of the first three bases of exon 14 (r.4358_4360del), leading to an in-frame deletion of the amino acid alanine at codon 1,453 (p.Ala1453del) FALSE Skipping of exon 12 21735045 Menéndez et al., 2012
BRCA1 Mutations predicted to alter splicing missense, splice, intron Splice leads to skipping of exon 12 and deletion of G 17:g.41234420del 17,41234420,41234420,C,- ENST00000357654 ENST00000357654:c.4357+1delG p.X1453_splice Splice_Site p.A1453Qfs*3 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del Can also be a a skipping of exon 13, although in the case of c.4357+1delG this aberrant band is observed in a lower proportion; this frameshift deletion is predicted to generate a premature stop codon (p.Arg1397TyrfsX2) FALSE Deletion of a guanine at the last base of exon 12 (r.4357del) because of the use of a cryptic donor splice site created by the DNA mutation 21735045 Menéndez et al., 2012
BRCA1 Mutations predicted to alter splicing missense, splice, intron Splice leads to skipping of exon 13 17:g.41228504C>A 17,41228504,41228504,C,A ENST00000357654 ENST00000357654:c.4484+1G>T p.X1495_splice Splice_Site p.A1453Gfs*10 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE This mutation arises in the invariant guanine in the consensus sequence of the 5' donor splice site of exon 13. cDNA analysis showed that this mutation abolishes the natural 5_ splice site of exon 13, causing complete deletion of this exon (r.4358_4484del) 21735045 Menéndez et al., 2012
BRCA1 Mutations predicted to alter splicing missense, splice, intron Splice leads to skipping of exon 16 and insertion of 153 bp of intron 16 17:g.41219622T>C 17,41219622,41219622,T,C ENST00000357654 ENST00000357654:c.5074+3A>G p.*1692* Splice_Region p.D1692Gfs*15 Splice_Exon_Skip_Frame_Shift Frame_Shift_Ins Can also be a skipping of exon 17 (r.4987_5074del), which is predicted to lead to the truncated proteins p.Val1665SerfsX8 FALSE The BRCA1 c.5074+3A>G variant was identified in a woman with bilateral breast cancer; her mother, who was diagnosed with breast cancer at age 53 and with colorectal cancer at age 68, carried the same variant. RNA analysis of this variant shows an insertion of the first 153 bp of intron 16 (r.5074_5075ins5074+1_5074+153). the pathogenicity of this mutation may derive from the splicing anomalies detected and is supported by the co-segregation with breast cancer observed in this family. 21735045 Menéndez et al., 2012
BRCA2 Mutations at canonical splice sites predicted to alter splicing splice, intron Splice leads to frameshift 13:g.32900634A>G 13,32900634,32900634,A,G ENST00000380152 ENST00000380152.3:c.517-2A>G p.X173_splice Splice_Site p.G173Sfs*17 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE germline 31843900 Casadei et al., 2019 0 0 0 70067 587 0 0 0 10953 1 0 0 0 60702 532 0 0 0 87119 221
BRCA2 Mutations at canonical splice sites predicted to alter splicing splice, intron Splice leads to frameshift 13:g.32931878G>A 13,32931878,32931878,G,A ENST00000380152 ENST00000380152.3:c.7618-1G>A p.X2540_splice Splice_Site p.L2540Qfs*10 Splice_Exon_Shortening_Frame_Shift Frame_Shift_Del FALSE germline 31843900 Casadei et al., 2019 0 0 0 70067 587 0 0 0 10953 1 0 0 0 60702 532 0 0 0 87119 221
BRCA2 Mutations at canonical splice sites predicted to alter splicing splice, intron Splice leads to frameshift 13:g.32954050G>A 13,32954050,32954050,G,A ENST00000380152 ENST00000380152.3:c.9117G>A p.X3039_splice Splice_Region p.V2985Gfs*3 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE germline 31843900 Casadei et al., 2019 0 0 0 70067 587 0 0 0 10953 1 0 0 0 60702 532 0 2 0 87119 221
BRCA2 c.6937+594T>G splice, intron Mutation in deep intron region creates a cryptic exon between exon 12 and 13 Found in patients with breast and ovarian cancer family history 13:g.32919384T>G 13,32919384,32919384,T,G ENST00000380152 ENST00000380152.3:c.6937+594T>G p.*2313* Intron p.G2313Gfs*9 Splice_Exon_Extension_Frame_Shift Frame_Shift_Ins FALSE 22753590 Anczuków et al., 2012
BRCA2 c.517-1G>A splice, intron, missense Splice leads to exon 7 skip 13:g.32900635G>A 13,32900635,32900635,G,A ENST00000380152 ENST00000380152.3:c.517-1G>A p.X173_splice Splice_Site p.G173Sfs*19 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del Activate a cryptic donor splice site that leads to the skipping of most of exon 6 and all of exon 7 (r.478_631del). This transcript is predicted to lead to a truncated protein (p.Val160SerfsX19) FALSE Leads to a skipping of exon 7 (r.517_631del) 21735045 Menéndez et al., 2012
BRCA2 c.1763A>G splice, intron, missense Splice leads to frameshift delins 13:g.32907378A>G 13,32907378,32907378,A,G ENST00000380152 ENST00000380152.3:c.1763A>G p.N588S Missense_Mutation p.N588_G637delinsS Splice_Exon_Shortening_In_Frame In_Frame_Del FALSE Identified in a woman diagnosed with breast cancer at age 31. This variant creates a new cryptic donor site, which leads to an alternative transcript consisting of an in-frame deletion of 147 nucleotides (r.1763_1909del) that, in turn, produces an in-frame deletion of 49 amino acids with the insertion of a serine (p.Asn588_Gly637delinsSer) 21735045 Menéndez et al., 2012
BRCA2 c.8332-1G>A splice, intron, missense Splice leads to frameshift delins 13:g.32944538G>A 13,32944538,32944538,G,A ENST00000380152 ENST00000380152.3:c.8332-1G>A p.X2778_splice Splice_Site p.I2778Yfs*15 Splice_Exon_Shortening_Frame_Shift Frame_Shift_Del FALSE This mutation arises in the invariant dinucleotide in the consensus sequence of the 3_ acceptor splice site of exon 19. cDNA analysis of the mutation showed that this mutation abolishes the natural 3_ splice site of exon 19 and leads to the activation of a cryptic splice site 14 bp downstream. Consequently, the mutated transcript shows a 14-bp deletion at the beginning of exon 19 (r.8332_8345del). 21735045 Menéndez et al., 2012
BRCA2 c.8954-15T>G splice, intron, missense Splice leads to frameshift delins 13:g.32953872T>G 13,32953872,32953872,T,G ENST00000380152 ENST00000380152.3:c.8954-15T>G p.*2985* Splice_Region p.V2985Afs*8 Splice_Exon_Extension_Frame_Shift Frame_Shift_Ins FALSE It creates a new cryptic donor site that leads to an alternative transcript with an insertion of the last 14 nucleotides of intron 22 (r.8953_8954ins8954-14_8954-1), generating a truncated protein (p.Val2985AlafsX8). Segregation analysis showed that the two sisters with breast cancer (diagnosed at 29 and 40 years old, respectively) are carriers of this variant, which was inherited from their unaffected father whose history is non-informative of HBOCS. 21735045 Menéndez et al., 2012
BRCA2 c.8954-5A>G splice, intron, missense Splice leads to frameshift delins 13:g.32953882A>G 13,32953882,32953882,A,G ENST00000380152 ENST00000380152.3:c.8954-5A>G p.X2985_splice Splice_Region p.V2985Dfs*34 Splice_Exon_Extension_Frame_Shift Frame_Shift_Ins FALSE It creates a novel cryptic donor site that leads to an alternative transcript with an insertion of the last four nucleotides of intron 22 (r.8953_8954ins8954-4_8954-1), generating a truncated protein (p.Val2985AspfsX34). The variant was observed in a young female patient with metachronic bilateral cancer diagnosed at 36 and 42 years who has no relative affected by tumors associated with HBOCS. 21735045 Menéndez et al., 2012
BRIP1 Mutations at canonical splice sites predicted to alter splicing splice Skip exon 5 Reported in individuals with breast and ovarian cancers 17:g.59926490C>T 17,59926490,59926490,C,T ENST00000259008 ENST00000259008.2:c.507G>A p.X169_splice Splice_Region p.D127Dfs*1 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del TRUE germline This silent sequence change affects codon 169 of the BRIP1 mRNA and does not change the encoded amino acid sequence (p.Gln169=). This variant falls at the last nucleotide of BRIP1 exon 5. This variant is absent from large population databases (1000 Genomes, ESP, and gnomAD), and has been reported in the literature in individuals with breast and ovarian cancers (PMID: 29368626). An experimental study using patient RNA showed that this variant led to skipping of exon 5 and a prematurely truncated protein product (PMID: 29368626). In summary, although additional studies are required to fully establish its clinical significance, this BRIp1 c.507G>A p.Gln169= variant is classified as likely pathogenic. Heterozygous pathogenic variants in BRIP1 have been associated with an increased risk of ovarian cancer (PMID: 26315354, 2196457) and may increase the risk of breast cancer (PMID: 17033622). Biallelic mutations in BRIP1 have been associated with Fanconi Anemia, an autosomal recessive condition characterized by physical abnormalities, bone marrow failure, and increased risk of malignancy. If a BRIP1 mutation carrier's partner is heterozygous for a pathogenic BRIP1 mutation, there is a 25% risk that each child would be affected by Fanconi Anemia. 29368626 Weber-Lassalle et al., 2018 0 0 0 70067 195 0 0 0 10953 0 0 0 0 60702 156 0 0 0 87119 163
BRIP1 Mutations at canonical splice sites predicted to alter splicing splice Skip exon 5 Reported in individuals with breast and ovarian cancers 17:g.59938807C>T 17,59938807,59938807,C,T ENST00000259008 ENST00000259008.2:c.93+1G>A p.X31_splice Splice_Site p.M1_S31del Splice_Exon_Skip_Non_Start In_Frame_Del FALSE germline 31843900 Casadei et al., 2019 0 0 0 70067 195 0 0 0 10953 0 0 0 0 60702 156 0 0 0 87119 163
CDH1 Mutations at canonical splice sites predicted to alter splicing missense, splice Splice leads to frameshift(exon 11) and nonsense(exon 10) 16:g.68849663G>A 16,68849663,68849663,G,A ENST00000261769 ENST00000261769.5:c.1565+1G>A p.X522_splice Splice_Site p.T523* Splice_Exon_Extension_Nonsense Nonsense_Mutation FALSE germline 31843900 Casadei et al., 2019 0 12 0 70067 818 0 0 2 10953 0 0 11 0 60702 729 0 0 0 87119 170
CDH1 Mutations at canonical splice sites predicted to alter splicing missense, splice Splice leads to frameshift(exon 11) and nonsense(exon 10) 16:g.68853328G>A 16,68853328,68853328,G,A ENST00000261769 ENST00000261769.5:c.1711G>A p.G571S Missense_Mutation p.Y523Ffs*15 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE germline 31843900 Casadei et al., 2019 0 1 0 70067 818 0 0 0 10953 0 0 1 0 60702 729 0 0 0 87119 170
CHEK2 Mutations at canonical splice sites predicted to alter splicing splice Splice leads to frameshift 22:g.29121230C>T 22,29121230,29121230,C,T ENST00000328354 ENST00000328354.6:c.444+1G>A p.X148_splice Splice_Site p.E149Ifs*5 Splice_Exon_Extension_Frame_Shift Frame_Shift_Ins FALSE germline 31843900 Casadei et al., 2019 0 1 0 70067 98 0 0 0 10953 0 0 1 0 60702 86 0 0 0 87119 66
PALB2 Mutations at canonical splice sites predicted to alter splicing splice Splice leads to exon 9 or exon 6 skipping 16:g.23634452C>G 16,23634452,23634452,C,G ENST00000261584 ENST00000261584.4:c.2835-1G>C p.X945_splice Splice_Site p.A946_G999del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE germline 31843900 Casadei et al., 2019 0 0 0 70067 18 0 0 0 10953 0 0 0 0 60702 20 0 0 0 87119 11
PALB2 Mutations at canonical splice sites predicted to alter splicing splice Splice leads to exon 9 or exon 6 skipping 16:g.23640597C>A 16,23640597,23640597,C,A ENST00000261584 ENST00000261584.4:c.2515-1G>T p.X839_splice Splice_Site p.T839_K862del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE germline 31843900 Casadei et al., 2019 0 0 0 70067 18 0 0 0 10953 0 0 0 0 60702 20 0 0 0 87119 11
RAD51D Mutations at canonical splice sites predicted to alter splicing splice Splice leads to frameshift exon truncation 17:g.33428057T>A 17,33428057,33428057,T,A ENST00000590016 ENST00000590016.1:c.964-2A>T p.X302_splice Splice_Site p.P322Vfs*5 Splice_Exon_Shortening_Frame_Shift Frame_Shift_Del FALSE germline 31843900 Casadei et al., 2019 0 0 0 70067 2 0 0 0 10953 0 0 0 0 60702 2 0 0 0 87119 6
MLH1 Last nucleotide of exon 15;Alterations on the ESE motifs cause deletion of exons splice Skipping of exon 15 and leads to an out-of-frame transcript and premature protein truncation; Alters number of ESEs affecting transcription In Lynch syndrome colorectal cancer and multiple cancer types 3:g.37083822G>A 3,37083822,37083822,G,A ENST00000231790 ENST00000231790.2:c.1731G>A p.X577_splice Splice_Region p.S556Rfs*13 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del TRUE germline The heterozygous germline variant, MLH1 c.1731G>A (p.Ser577Ser), results in a silent mutation and occurs at the last nucleotide of exon 15. This variant is absent from the major population databases (1000G, ESP and gnomAD). It is a well known pathogenic variant that has been reported in several individuals and families with Lynch syndrome (PMID: 16341550, 15849733, 20223024, 26300997, 14635101, 16216036, 16395668, 19669161). Experimental studies using mRNA isolated from patients blood as well as a reporter minigene assay showed that this variant results in the skipping of exon 15 and leads to an out-of-frame transcript and premature protein truncation (PMID: 16341550, 18561205, 16451135). In summary, based on the previous reports of this variant in individuals with MLH1 associated cancers and its truncating effect on the protein, this variant meets our criteria to be classified as pathogenic. Lynch syndrome is an autosomal dominant condition that confers an increased risk for colorectal cancer and endometrial cancers as well as other cancers. There is a 50% chance that each child would inherit this variant from a carrier parent. 16341550;18561205;16451135 Pagenstecher et al., 2006;Tournier et al., 2008;Kurzawski et al., 2006 0 0 0 70067 9 0 0 0 10953 0 0 0 0 60702 8 0 6 0 87119 53
MLH1 Last nucleotide of exon 15;Alterations on the ESE motifs cause deletion of exons splice Skipping of exon 15 and leads to an out-of-frame transcript and premature protein truncation; Alters number of ESEs affecting transcription In Lynch syndrome colorectal cancer and multiple cancer types 3:g.37059048C>T 3,37059048,37059048,C,T ENST00000231790 ENST00000231790.2:c.842C>T p.A281V Missense_Mutation p.H264Lfs*2 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE Alterations on the ESE motifs cause deletion of exons, affects splicing across multiple cancer types 16995940 Lastella et al., 2006 0 1 0 70067 9 0 0 1 10953 0 0 1 0 60702 8 0 0 0 87119 53
MLH1 Last nucleotide of exon 15;Alterations on the ESE motifs cause deletion of exons splice Skipping of exon 15 and leads to an out-of-frame transcript and premature protein truncation; Alters number of ESEs affecting transcription In Lynch syndrome colorectal cancer and multiple cancer types 3:g.37090087G>C 3,37090087,37090087,G,C ENST00000231790 ENST00000231790.2:c.1976G>C p.R659P Missense_Mutation p.E633_E663del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE Alterations on the ESE motifs cause deletion of exons, affects splicing across multiple cancer types 16995940 Lastella et al., 2006 0 0 0 70067 9 0 0 0 10953 0 0 0 0 60702 8 0 0 0 87119 53
MLH1 Last nucleotide of exon 15;Alterations on the ESE motifs cause deletion of exons splice Skipping of exon 15 and leads to an out-of-frame transcript and premature protein truncation; Alters number of ESEs affecting transcription In Lynch syndrome colorectal cancer and multiple cancer types 3:g.37050394C>T 3,37050394,37050394,C,T ENST00000231790 ENST00000231790.2:c.543C>T p.X181_splice Splice_Region p.G181Gfs*20 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE germline 28334867 Yamaguchi et al., 2017 0 0 0 70067 9 0 0 0 10953 0 0 0 0 60702 8 0 1 0 87119 53
MLH1 c.546-2A>G splice Skipping of exon 7 In colorectal cancer or HNPCC-associated cancers (endometrium, small bowel, urinary tract) 3:g.37053309A>G 3,37053309,37053309,A,G ENST00000231790 ENST00000231790.2:c.546-2A>G p.X182_splice Splice_Site p.R84Sfs*5 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE germline 16451135 Kurzawski et al., 2006
MLH1 c.677G>T missense Skipping of exon 8 In colorectal cancer or HNPCC-associated cancers (endometrium, small bowel, urinary tract) 3:g.37053590G>T 3,37053590,37053590,G,T ENST00000231790 ENST00000231790.2:c.677G>T p.R226L Missense_Mutation p.Q197Rfs*7 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE germline 12362047;16451135 Kurzawski et al., 2002;Kurzawski et al., 2006
MLH1 c.883A>C missense Skipping of exon 10 In colorectal cancer or HNPCC-associated cancers (endometrium, small bowel, urinary tract) 3:g.37059089A>C 3,37059089,37059089,A,C ENST00000231790 ENST00000231790.2:c.883A>C p.S295R Missense_Mutation p.H264Lfs*1 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE germline 12362047;16451135 Kurzawski et al., 2002;Kurzawski et al., 2006
MLH1 c.1409+1G>C splice Skipping of exon 12 In colorectal cancer or HNPCC-associated cancers (endometrium, small bowel, urinary tract) 3:g.37067499G>C 3,37067499,37067499,G,C ENST00000231790 ENST00000231790.2:c.1409+1G>C p.X470_splice Splice_Site p.T347Kfs*7 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE germline 12362047;16451135 Kurzawski et al., 2002;Kurzawski et al., 2006
EGFR 5 bases upstream from the 5' end of exon 20 (7:g.55248980_55248981insTCCAGGAAGCCT) splice Inset a repeated sequence from 55248980-55248992 Recurrent in lung cancer, can be linked to Level 1 TKIs 7:g.55248980_55248981insTCCAGGAAGCCT 7,55248980,55248981,-,TCCAGGAAGCCT ENST00000275493 ENST00000275493.2:c.2284-5_2290dup p.X762_splice Splice_Region p.A763_Y764insFQEA Splice_Exon_Extension_In_Frame In_Frame_Ins TRUE 31715539 Sousa et al., 2020 0 9 0 70067 1512 0 0 0 10953 1 0 6 0 60702 1346 0 0 0 87119 306
TP53 c.375+5G mutations flanking exon 4 splice Splice leads to whole exon 4 skipping inframe deletion or partial exon 4 skipping frameshift Recurrent in many cancer types and results in P53 protein loss of function 17:g.7579307C>A 17,7579307,7579307,C,A ENST00000269305 ENST00000269305.4:c.375+5G>T p.X125_splice Splice_Region p.S33_T125del Splice_Exon_Skip_In_Frame In_Frame_Del Partial exon 4 skip, p.G59Vfs*23, Splice_Exon_Shortening_Frame_Shift TRUE 34505757 Chui et al., 2021 0 0 0 70067 1217 0 0 0 10953 1 0 0 0 60702 1109 0 49 0 87119 283
TP53 c.375G>T splice Splice leads to whole exon 4 skipping inframe deletion or partial exon 4 skipping frameshift Recurrent in many cancer types and results in P53 protein loss of function 17:g.7579312C>A 17,7579312,7579312,C,A ENST00000269305 ENST00000269305.4:c.375G>T p.X125_splice Splice_Region p.S33_T125del Splice_Exon_Skip_In_Frame In_Frame_Del TRUE germline The heterozygous germline variant, TP53 c.375G>T (Thr125=), is located at the last nucleotide of exon 4 of the TP53 gene. This variant is absent from large population databases (1000 Genomes, ESP, and gnomAD). It has been reported in a family with Li Fraumeni syndrome (PMID: 11420676). In vitro studies and analysis of RNA from patient cells demonstrated that this variant leads to aberrant splicing (PMID: 11420676, 25730903). Two other variants at this position (c.375G>A and c.375G>C) have been reported in individuals and families with Li Fraumeni syndrome (PMID: 9242456, 10864200, 11420676, 24382691, 31105275). In summary, although additional studies are required to fully establish its clinical significance, based on its previous report in an individual with Li Fraumeni syndrome and its demonstrated impact on splicing, this c.375G>T (p.?) variant is classified as likely pathogenic. Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome associated with an increased risk of tumors including soft tissue sarcoma, osteosarcoma, pre-menopausal breast cancer, brain tumors, adrenocortical carcinoma (ACC), and leukemias (http://www.ncbi.nlm.nih.gov/books/NBK1311/). 11420676 Varley et al., 2001 0 0 0 70067 1217 0 0 25 10953 1 0 0 0 60702 1109 0 124 2 87119 283
F11 Alterations in Exon Splice Enhancement Sites (ESE) affecting multiple exons missense Alters number of ESEs affecting transcription and causing aberrant splicing Largely found in cancer-related thrombosis 4:g.187208954G>A 4,187208954,187208954,G,A ENST00000403665 ENST00000403665.2:c.1693G>A p.E565K Missense_Mutation p.D526_G572del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 21718436 Zucker et al., 2011 0 0 0 70067 0 0 0 0 10953 0 0 0 0 60702 0 0 0 0 87119 0
F11 Alterations in Exon Splice Enhancement Sites (ESE) affecting multiple exons missense Alters number of ESEs affecting transcription and causing aberrant splicing Largely found in cancer-related thrombosis 4:g.187201659G>A 4,187201659,187201659,G,A ENST00000403665 ENST00000403665.2:c.1060G>A p.G350R Missense_Mutation p.K343_E379del Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE 21718436 Zucker et al., 2011 0 0 0 70067 0 0 0 1 10953 0 0 0 0 60702 0 0 0 0 87119 0
F11 Alterations in Exon Splice Enhancement Sites (ESE) affecting multiple exons missense Alters number of ESEs affecting transcription and causing aberrant splicing Largely found in cancer-related thrombosis 4:g.187197405C>T 4,187197405,187197405,C,T ENST00000403665 ENST00000403665.2:c.616C>T p.P206S Missense_Mutation p.A199_R252del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 21718436 Zucker et al., 2011 0 0 0 70067 0 0 0 0 10953 0 0 0 0 60702 0 0 0 0 87119 0
MSH2 Alterations on the ESE motifs cause skipping of exons missense Alters number of ESEs affecting transcription Affects splicing across multiple cancer types 2:g.47641421C>T 2,47641421,47641421,C,T ENST00000233146 ENST00000233146.2:c.806C>T p.S269L Missense_Mutation p.V265_Q314del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 16995940 Lastella et al., 2006 0 0 0 70067 22 0 0 0 10953 0 0 0 0 60702 17 0 0 0 87119 21
MSH2 Alterations on the ESE motifs cause skipping of exons missense Alters number of ESEs affecting transcription Affects splicing across multiple cancer types 2:g.47641430C>T 2,47641430,47641430,C,T ENST00000233146 ENST00000233146.2:c.815C>T p.A272V Missense_Mutation p.V265_Q314del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE 16995940 Lastella et al., 2006 0 5 1 70067 22 0 0 0 10953 0 0 3 1 60702 17 0 0 0 87119 21
MSH2 Alterations on the ESE motifs cause skipping of exons missense Alters number of ESEs affecting transcription Affects splicing across multiple cancer types 2:g.47693802G>T 2,47693802,47693802,G,T ENST00000233146 ENST00000233146.2:c.1516G>T p.D506Y Missense_Mutation p.G504Afs*3 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE 16995940 Lastella et al., 2006 0 2 0 70067 22 0 0 0 10953 0 0 1 0 60702 17 0 0 0 87119 21
MSH2 Alterations on the ESE motifs cause skipping of exons missense Alters number of ESEs affecting transcription Affects splicing across multiple cancer types 2:g.47693886C>T 2,47693886,47693886,C,T ENST00000233146 ENST00000233146.2:c.1600C>T p.R534C Missense_Mutation p.G504Afs*3 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE 16995940 Lastella et al., 2006 0 4 0 70067 22 0 0 0 10953 0 0 4 0 60702 17 0 0 0 87119 21
MSH2 c.942+3A>T mutation flanking exon 5 splice Skipping of exon 5 Reported in families with colorectal cancer 2:g.47641560A>T 2,47641560,47641560,A,T ENST00000233146 ENST00000233146.2:c.942+3A>T p.X314_splice Splice_Region p.V265_Q314del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE germline 33259954;12362047;16451135 Oldfield et al., 2021;Kurzawski et al., 2002;Kurzawski et al., 2006
MSH2 c.1661+5G>C splice Skipping of exon 10 Reported in families with colorectal cancer, potentially specific for Polish families 2:g.47693952G>C 2,47693952,47693952,G,C ENST00000233146 ENST00000233146.2:c.1661+5G>C p.*554* Splice_Region p.G504Afs*3 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE germline 33259954;12362047;16451135 Oldfield et al., 2021;Kurzawski et al., 2002;Kurzawski et al., 2006
MSH2 c.645+1G>T splice Skipping of exon 3 In colorectal cancer or HNPCC-associated cancers (endometrium, small bowel, urinary tract) 2:g.47637512G>T 2,47637512,47637512,G,T ENST00000233146 ENST00000233146.2:c.645+1G>T p.X215_splice Splice_Site p.A123_Q215del Splice_Exon_Skip_In_Frame In_Frame_Del FALSE germline 12362047;16451135 Kurzawski et al., 2002;Kurzawski et al., 2006
MSH2 c.2210+1G>C splice Skipping of exon 13 In colorectal cancer or HNPCC-associated cancers (endometrium, small bowel, urinary tract) 2:g.47703711G>C 2,47703711,47703711,G,C ENST00000233146 ENST00000233146.2:c.2210+1G>C p.X737_splice Splice_Site p.G669Gfs*7 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE germline 12362047;16451135 Kurzawski et al., 2002;Kurzawski et al., 2006
MSH2 c.2634+1G>A splice Skipping of exon 15 and leads to an out-of-frame transcript and premature protein truncation; Alters number of ESEs affecting transcription In colorectal cancer or HNPCC-associated cancers (endometrium, small bowel, urinary tract) 2:g.47708011G>A 2,47708011,47708011,G,A ENST00000233146 ENST00000233146.2:c.2634+1G>A p.X878_splice Splice_Site p.G820Afs*2 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE germline 12362047;16451135 Kurzawski et al., 2002;Kurzawski et al., 2006
RB1 c.1206C>T mutation on exon 12 synonymous Disrupting the splicing enhancer element and caused skipping of exon 12 Reported in an individual with unilateral retinoblastoma 13:g.48947619C>T 13,48947619,48947619,C,T ENST00000267163 ENST00000267163.4:c.1206C>T p.S402= Silent p.R376Rfs*4 Splice_Exon_Skip_Frame_Shift Frame_Shift_Del FALSE This heterozygous RB1 c.1206C>T variant is a synonymous variant that does not alter the amino acid at this position (p.Ser402=). This variant has been identified in 3/30442 South Asian chromosomes by the Genome Aggregation Database (gnomAD: http://gnomad.broadinstitute.org). It has been reported in an individual with unilateral retinoblastoma and was demonstrated to cause abnormal splicing based on patient RNA studies (PMID 21763628). In our patient (DMG19-4863) with unilateral retinoblastoma, tumor analysis identified somatic biallelic mutations (two somatic hits) in RB1 (DMG internal data). In summary, based on the currently available data, the clinical significance of the RB1 c.1206C>T (p.Ser402=) variant is uncertain. 21763628 Ahani et al., 2011
CDH1 last nucleotide of exon 7 splice Altered the exon 7 boundary, producing 7 bp insertions of the intron sequences Reported in an individual affected with diffuse gastric cancer 16:g.68845762G>A 16,68845762,68845762,G,A ENST00000261769 ENST00000261769.5:c.1008G>A p.X336_splice Splice_Region p.S337Vfs*14 Splice_Exon_Extension_Frame_Shift Frame_Shift_Ins Can also be 25, 42, 150 bp intron 7 insertion, and whole intron 7 insertions FALSE The heterozygous germline variant, CDH1 c.1008G>A (p.Glu336=) is located at the last nucleotide of exon 7 of the CDH1 gene. This variant is absent from large population databases (1000 Genomes, ESP, and gnomAD) and has been reported in an individual affected with diffuse gastric cancer (PMID: 27730413). Experimental studies and analysis of RNA demonstrated that this variant leads to aberrant splicing (PMID: 8127895, 18427545). Additionally, a different variant at this position (c.1008G>T) has been reported in a family affected with hereditary diffuse gastric cancer (PMID: 9537325, 19725995). In summary, although additional studies are required to fully establish its clinical significance, this c.1008G>A variant is classified as likely pathogenic.
Pathogenic variants in CDH1 cause hereditary diffuse gastric cancer which is an autosomal dominant characterized by susceptibility to diffuse gastric cancer (also referred to as signet ring carcinoma or isolated cell-type carcinoma) and lobular breast cancer (https://www.ncbi.nlm.nih.gov/books/NBK1139/). Relatives of an individual with a pathogenic CDH1 variant have up-to 50% probability of carrying the same variant, and carriers are at an increased risk of developingCDH1-associated disease. 8127895;18427545 Oda et al., 1994;Karam et al., 2008