ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1928A>G (p.Gln643Arg)

gnomAD frequency: 0.00001  dbSNP: rs760629688
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000463007 SCV000551970 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-12-18 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 643 of the PMS2 protein (p.Gln643Arg). This variant is present in population databases (rs760629688, gnomAD 0.06%). This missense change has been observed in individual(s) with Lynch syndrome (PMID: 24710284). ClinVar contains an entry for this variant (Variation ID: 411037). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is not expected to disrupt PMS2 function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000573574 SCV000663528 likely benign Hereditary cancer-predisposing syndrome 2021-06-11 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.
Fulgent Genetics, Fulgent Genetics RCV000765955 SCV000897376 uncertain significance Mismatch repair cancer syndrome 1; Lynch syndrome 4 2018-10-31 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000573574 SCV000911418 likely benign Hereditary cancer-predisposing syndrome 2016-05-30 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001821289 SCV002068805 uncertain significance not specified 2018-03-26 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004001875 SCV004844118 likely benign Lynch syndrome 2024-05-14 criteria provided, single submitter clinical testing

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