ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.874A>T (p.Thr292Ser)

gnomAD frequency: 0.00003  dbSNP: rs104895022
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000114837 SCV000149455 uncertain significance not provided 2022-10-03 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26333163, 18822302, 21120944, 20805886)
Ambry Genetics RCV000115546 SCV000216817 likely benign Hereditary cancer-predisposing syndrome 2023-05-04 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV000699802 SCV000828529 benign Hereditary nonpolyposis colorectal neoplasms 2023-10-24 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000115546 SCV001355777 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-29 criteria provided, single submitter clinical testing This missense variant replaces threonine with serine at codon 292 of the MSH2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). To our knowledge, this variant has not been reported in individuals affected with MSH2-related disorders in the literature. This variant has been identified in 7/251178 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001800400 SCV002046321 uncertain significance not specified 2020-10-16 criteria provided, single submitter clinical testing
Harris Lab, University of Minnesota RCV000114837 SCV000148732 not provided not provided no assertion provided not provided

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