ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.2224G>A (p.Asp742Asn)

gnomAD frequency: 0.00001  dbSNP: rs879254183
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236064 SCV000293743 uncertain significance not provided 2022-11-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Identified in patients with advanced cancer, not otherwise specified (Mandelker et al., 2017); This variant is associated with the following publications: (PMID: 28873162)
Invitae RCV000556812 SCV000625363 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-10-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV000564620 SCV000662242 likely benign Hereditary cancer-predisposing syndrome 2022-04-11 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Color Diagnostics, LLC DBA Color Health RCV000564620 SCV001341221 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-14 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with asparagine at codon 742 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). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251324 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.
Baylor Genetics RCV003469187 SCV004196337 uncertain significance Lynch syndrome 1 2023-07-28 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003998917 SCV004825769 uncertain significance Lynch syndrome 2023-05-31 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with asparagine at codon 742 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). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251324 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.

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