ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.645+2T>C (rs876658996)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520097 SCV000618558 likely pathogenic not provided 2017-11-06 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.645+2T>C or IVS3+2T>C and consists of a T>C nucleotide substitution at the +2 position of intron 3 of the MSH2 gene. This 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 currently available information, we consider MSH2 c.645+2T>C to be a likely pathogenic variant.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000606441 SCV000712752 pathogenic Lynch syndrome 2016-12-21 criteria provided, single submitter clinical testing The c.645+2T>C variant in MSH2 has not been previously reported in individuals w ith Lynch Syndrome or in large population studies. This variant occurs in the in variant region (+/- 1,2) of the splice consensus sequence and is predicted to ca use altered splicing leading to an abnormal or absent protein. Heterozygous loss of function of the MSH2 gene is an established disease mechanism in individuals with Lynch syndrome. In summary, this variant meets criteria to be classified a s pathogenic for Lynch syndrome in an autosomal dominant manner based upon absen ce from the general population and predicted impact to the protein.

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