ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.827G>A (p.Cys276Tyr) (rs1554300806)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000630104 SCV000751060 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2017-11-03 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 276 of the PMS2 protein (p.Cys276Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PMS2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001000746 SCV001157794 uncertain significance not specified 2018-08-12 criteria provided, single submitter clinical testing The PMS2 c.827G>A; p.Cys276Tyr variant, to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 525797). This variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The cysteine at codon 276 is moderately conserved but computational analyses (SIFT: Damaging, PolyPhen-2: Benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Cys276Tyr variant is uncertain at this time.

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