ClinVar Miner

Submissions for variant NM_000535.6(PMS2):c.682G>A (p.Gly228Ser) (rs376258383)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115700 SCV000217475 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000115700 SCV000902891 benign Hereditary cancer-predisposing syndrome 2016-09-14 criteria provided, single submitter clinical testing
Counsyl RCV000663188 SCV000786360 uncertain significance Hereditary nonpolyposis colorectal cancer type 4 2018-04-20 criteria provided, single submitter clinical testing
GeneDx RCV000212847 SCV000149609 uncertain significance not provided 2018-08-10 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.682G>A at the cDNA level, p.Gly228Ser (G228S) at the protein level, and results in the change of a Glycine to a Serine (GGC>AGC). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. PMS2 Gly228Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the ATPase domain (Guarne 2001). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether PMS2 Gly228Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000472958 SCV000551937 uncertain significance Hereditary nonpolyposis colon cancer 2018-06-27 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 228 of the PMS2 protein (p.Gly228Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs376258383, ExAC 0.02%). This variant has not been reported in the literature in individuals with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 127794). 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: "Tolerated"; 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.
PreventionGenetics RCV000212847 SCV000806220 uncertain significance not provided 2017-09-01 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212847 SCV000889637 uncertain significance not provided 2018-02-21 criteria provided, single submitter clinical testing

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