ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.212-1G>A (rs267607914)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076394 SCV000107430 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Multifactorial likelihood analysis posterior probability >0.99
Ambry Genetics RCV000218216 SCV000278680 pathogenic Hereditary cancer-predisposing syndrome 2018-03-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
GeneDx RCV000202270 SCV000567721 pathogenic not provided 2017-08-29 criteria provided, single submitter clinical testing This pathogenic variant is denoted MSH2 c.212-1G>A or IVS1-1G>A and consists of a G>A nucleotide substitution at the -1 position of intron 1 of the MSH2 gene. The variant destroys a canonical splice acceptor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has been observed in at least three individuals with Lynch syndrome (Overbeek 2007, Ramsoekh 2008, De Lellis 2013), and is considered pathogenic.
Invitae RCV000696322 SCV000824877 likely pathogenic Hereditary nonpolyposis colon cancer 2018-11-20 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 1 of the MSH2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with colorectal cancer and bladder cancer (PMID: 17453009, 20591884, 24278394), and in an individual with clinical suspicion of Lynch syndrome (PMID: 18625694). ClinVar contains an entry for this variant (Variation ID: 90892). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202270 SCV000257169 pathogenic not provided no assertion criteria provided research

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