ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.457+1G>T

dbSNP: rs2104112957
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002341743 SCV002638532 likely pathogenic Hereditary cancer-predisposing syndrome 2018-02-20 criteria provided, single submitter clinical testing The c.457+1G>T intronic variant results from a G to T substitution one nucleotide after coding exon 2 of the MSH6 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001356829 SCV001552098 pathogenic Carcinoma of colon no assertion criteria provided clinical testing The MSH6 c.457+1G>T variant was not identified in the literature nor was it identified in dbSNP, ClinVar UMD-LSDB, Exome Aggregation Consortium (August 8th 2016) and Genome Aggregation Database (Feb 27, 2017). The c.457+1G>T variant is predicted to cause abnormal splicing because the nucleotide substitution occurs in the invariant region of the splice consensus sequence. In addition 4 out of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predicted a greater than 10% difference in splicing. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic.

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