ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1519A>G (p.Ser507Gly)

gnomAD frequency: 0.00001  dbSNP: rs63751028
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165919 SCV000216674 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-15 criteria provided, single submitter clinical testing The p.S507G variant (also known as c.1519A>G), located in coding exon 11 of the PMS2 gene, results from an A to G substitution at nucleotide position 1519. The serine at codon 507 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000532007 SCV000625534 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 507 of the PMS2 protein (p.Ser507Gly). 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: 186340). 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 with a negative predictive value of 80%. 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.
Color Diagnostics, LLC DBA Color Health RCV000165919 SCV000909653 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-09 criteria provided, single submitter clinical testing This missense variant replaces serine with glycine at codon 507 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PMS2-related disorders in the literature. 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.
GeneDx RCV001775646 SCV002012599 uncertain significance not provided 2019-11-15 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
All of Us Research Program, National Institutes of Health RCV003995464 SCV004844194 uncertain significance Lynch syndrome 2023-04-03 criteria provided, single submitter clinical testing This missense variant replaces serine with glycine at codon 507 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PMS2-related disorders in the literature. 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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