ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.982G>C (p.Ala328Pro)

gnomAD frequency: 0.00001  dbSNP: rs753237286
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000662549 SCV000785131 uncertain significance Lynch syndrome 1 2017-05-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV001019794 SCV001181199 likely benign Hereditary cancer-predisposing syndrome 2023-08-08 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 RCV001019794 SCV001355778 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-05 criteria provided, single submitter clinical testing This missense variant replaces alanine with proline at codon 328 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 reported in an individual affected with colorectal cancer (PMID: 11606497) and an individual affected with breast cancer (PMID: 26976419). This variant has been identified in 4/251454 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001229515 SCV001401962 benign Hereditary nonpolyposis colorectal neoplasms 2025-01-19 criteria provided, single submitter clinical testing
GeneDx RCV001584524 SCV001813455 uncertain significance not provided 2019-08-06 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Published functional studies suggest decreased repair efficiency in comparison to wild type (Kantelinen 2012); This variant is associated with the following publications: (PMID: 26976419, 22581703, 18470917, 25186627, 11606497)
Myriad Genetics, Inc. RCV000662549 SCV004018224 uncertain significance Lynch syndrome 1 2023-03-16 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
All of Us Research Program, National Institutes of Health RCV004004205 SCV004824520 uncertain significance Lynch syndrome 2024-05-14 criteria provided, single submitter clinical testing This missense variant replaces alanine with proline at codon 328 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 reported in an individual affected with colorectal cancer (PMID: 11606497) and an individual affected with breast cancer (PMID: 26976419). This variant has been identified in 4/251454 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 RCV000662549 SCV005053444 uncertain significance Lynch syndrome 1 2024-02-29 criteria provided, single submitter clinical testing

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