ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.904G>T (p.Val302Phe)

gnomAD frequency: 0.00001  dbSNP: rs755960629
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000477186 SCV000552032 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-01-09 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 302 of the PMS2 protein (p.Val302Phe). This variant is present in population databases (rs755960629, gnomAD 0.02%). This missense change has been observed in individual(s) with esophageal cancer, biliary tract cancer, and/or breast cancer (PMID: 30833958, 35449176, 36243179). ClinVar contains an entry for this variant (Variation ID: 411067). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 RCV000569989 SCV000663430 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-01 criteria provided, single submitter clinical testing The p.V302F variant (also known as c.904G>T) is located in coding exon 9 of the PMS2 gene. The valine at codon 302 is replaced by phenylalanine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 9. RNA studies have demonstrated that this alteration does not result in abnormal splicing in the set of samples tested (Ambry internal data). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000569989 SCV000686255 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-09 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001798841 SCV002042818 uncertain significance Breast and/or ovarian cancer 2020-11-04 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002481462 SCV002791729 uncertain significance Lynch syndrome 4; Mismatch repair cancer syndrome 4 2022-05-18 criteria provided, single submitter clinical testing

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