ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.139C>G (p.Leu47Val)

gnomAD frequency: 0.00002  dbSNP: rs766203500
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000205693 SCV000259856 likely benign Hereditary nonpolyposis colorectal neoplasms 2024-01-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV000575149 SCV000663454 likely benign Hereditary cancer-predisposing syndrome 2018-03-23 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Counsyl RCV000662464 SCV000784946 uncertain significance Lynch syndrome 4 2017-02-14 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000575149 SCV000910994 likely benign Hereditary cancer-predisposing syndrome 2016-12-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193970 SCV001363167 uncertain significance not specified 2019-01-18 criteria provided, single submitter clinical testing Variant summary: The variant, PMS2 c.139C>G (p.Leu47Val) results in a conservative amino acid change located in the DNA mismatch repair protein family, N-terminal domain and Histidine kinase/HSP90-like ATPase domain of the encoded protein sequence. Several in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.9e-05 in 240416 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.139C>G in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (uncertain significance (2) and Likely benign (1)). Based on the evidence outlined above, the variant was classified as uncertain significance.
Sema4, Sema4 RCV000575149 SCV002529790 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-23 criteria provided, single submitter curation
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University RCV003153480 SCV003843525 benign Ovarian cancer 2022-01-01 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000662464 SCV004019857 uncertain significance Lynch syndrome 4 2023-04-04 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
All of Us Research Program, National Institutes of Health RCV003997581 SCV004842154 likely benign Lynch syndrome 2023-11-30 criteria provided, single submitter clinical testing

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