ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1607A>G (p.Asn536Ser)

dbSNP: rs201722703
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000697547 SCV000826166 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-10-30 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000774570 SCV000908308 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-17 criteria provided, single submitter clinical testing This missense variant replaces asparagine with serine at codon 536 of the MSH2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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). This variant has been detected in an individual affected with juvenile polyposis who also carried a BMPR1A canonical splice site variant that could explain the disease phenotype (PMID: 30680046). This variant has been identified in 1/251342 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.
Ambry Genetics RCV000774570 SCV002709593 likely benign Hereditary cancer-predisposing syndrome 2022-03-21 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.
All of Us Research Program, National Institutes of Health RCV003999668 SCV004833926 uncertain significance Lynch syndrome 2023-11-02 criteria provided, single submitter clinical testing This missense variant replaces asparagine with serine at codon 536 of the MSH2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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). This variant has been detected in an individual affected with juvenile polyposis who also carried a BMPR1A canonical splice site variant that could explain the disease phenotype (PMID: 30680046). This variant has been identified in 1/251342 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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