ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.451C>G (p.Arg151Gly)

dbSNP: rs758561884
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Human Genetics Unit, University Of Colombo RCV000993767 SCV000928314 likely pathogenic Familial cancer of breast 2019-07-24 criteria provided, single submitter clinical testing This c.451C>G (p.Arg151Gly) variant in PMS2 has been seen in a patient having breast and ovarian cancer with a family history of breast cancer. This mutation is not found in global population frequency databases or in our internal exome database. In silico analysis concluded this variant as disease-causing. Recent studies have shown an association of PMS2 mutations with increased risk of breast cancer (PMID:29345684). According to ACMG criteria (2015), this variant can be classified as likely pathogenic (II). Evidence:PS4, PM1, PM2, PP4
Ambry Genetics RCV001022626 SCV001184384 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-14 criteria provided, single submitter clinical testing The p.R151G variant (also known as c.451C>G), located in coding exon 5 of the PMS2 gene, results from a C to G substitution at nucleotide position 451. The arginine at codon 151 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice acceptor site; however, direct evidence is unavailable. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV002535819 SCV003340241 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2022-04-16 criteria provided, single submitter clinical testing Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PMS2 protein function. This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 151 of the PMS2 protein (p.Arg151Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 638152). 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.
Baylor Genetics RCV003467323 SCV004205445 uncertain significance Lynch syndrome 4 2023-09-14 criteria provided, single submitter clinical testing

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