ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1277-1G>C (rs267607948)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076098 SCV000107120 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Interrupts canonical donor splice site
Ambry Genetics RCV001010704 SCV001170937 likely pathogenic Hereditary cancer-predisposing syndrome 2019-03-04 criteria provided, single submitter clinical testing The c.1277-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 8 of the MSH2 gene. This alteration has been reported in the germline of one German individual diagnosed with MSI-high colorectal cancer demonstrating the loss of MSH2 protein (Mangold E et al. J. Pathol., 2005 Dec;207:385-95). 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 acceptor 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.

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