ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1276+2T>C (rs267607953)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000202216 SCV000292623 pathogenic not provided 2018-10-23 criteria provided, single submitter clinical testing This pathogenic variant is denoted MSH2 c.1276+2T>C or IVS7+2T>C and consists of a T>C nucleotide substitution at the +2 position of intron 7 of the MSH2 gene. The variant destroys a canonical splice donor 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 not, to our knowledge, been published in the literature. Based on the current evidence, we consider MSH2 c.1276+2T>C to be pathogenic.
Invitae RCV000460835 SCV000548099 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-02-26 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 7 of the MSH2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs267607953, ExAC 0.002%). Disruption of this splice site has been observed in individuals affected with Lynch syndrome associated tumors (PMID: 16395668, 21642682, 19669161, 21520333, Invitae). ClinVar contains an entry for this variant (Variation ID: 218032). 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). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000492023 SCV000580619 pathogenic Hereditary cancer-predisposing syndrome 2018-10-29 criteria provided, single submitter clinical testing 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
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000202216 SCV000601428 pathogenic not provided 2016-12-23 criteria provided, single submitter clinical testing
Counsyl RCV000576479 SCV000677828 likely pathogenic Lynch syndrome I 2016-12-14 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202216 SCV000257131 likely pathogenic not provided no assertion criteria provided research

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