ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.328G>T (p.Ala110Ser) (rs767775907)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000220893 SCV000279857 uncertain significance not provided 2018-05-03 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.328G>T at the cDNA level, p.Ala110Ser (A110S) at the protein level, and results in the change of an Alanine to a Serine (GCT>TCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PMS2 Ala110Ser was not observed at a significant frequency in large population cohorts (Lek 2016). This variant is located in motif III of the ATPase domain (Guarne 2001). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether PMS2 Ala110Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000630099 SCV000751055 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-06-18 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 110 of the PMS2 protein (p.Ala110Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs767775907, ExAC 0.003%). This variant has not been reported in the literature in individuals with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 234814). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Fulgent Genetics,Fulgent Genetics RCV000765969 SCV000897390 uncertain significance Turcot syndrome; Hereditary nonpolyposis colorectal cancer type 4 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV001019709 SCV001181101 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-11 criteria provided, single submitter clinical testing Insufficient evidence
Color RCV001019709 SCV001360038 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-06 criteria provided, single submitter clinical testing

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