ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.10C>A (p.Gln4Lys)

gnomAD frequency: 0.00001  dbSNP: rs878853797
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000227770 SCV000284091 benign Hereditary nonpolyposis colorectal neoplasms 2024-10-13 criteria provided, single submitter clinical testing
GeneDx RCV000480195 SCV000565181 uncertain significance not provided 2023-12-08 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; Published functional studies suggest a neutral effect of mismatch repair (MMR) function (PMID: 33357406); This variant is associated with the following publications: (PMID: 18822302, 21120944, 32906206, 33471991, 33357406)
Ambry Genetics RCV000563870 SCV000662219 likely benign Hereditary cancer-predisposing syndrome 2023-02-15 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 RCV000563870 SCV000684903 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-23 criteria provided, single submitter clinical testing This missense variant replaces glutamine with lysine at codon 4 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with breast cancer in the literature (PMID: 33471991). This variant has not been identified 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.
Sema4, Sema4 RCV000563870 SCV002528812 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-09 criteria provided, single submitter curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002465579 SCV002760628 uncertain significance not specified 2023-08-15 criteria provided, single submitter clinical testing
Baylor Genetics RCV003469135 SCV004193920 uncertain significance Lynch syndrome 1 2024-03-18 criteria provided, single submitter clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000563870 SCV004228036 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-21 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003998750 SCV004826205 uncertain significance Lynch syndrome 2024-09-23 criteria provided, single submitter clinical testing This missense variant replaces glutamine with lysine at codon 4 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with breast cancer in the literature (PMID: 33471991). This variant has not been identified 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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