ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2149G>A (p.Val717Met) (rs201671325)

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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000417397 SCV000149585 likely benign not specified 2018-01-15 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000115676 SCV000187235 likely benign Hereditary cancer-predisposing syndrome 2018-12-28 criteria provided, single submitter clinical testing Intact protein function observed in appropriate functional assay(s);Co-occurence with mutation in same gene (phase unknown);Subpopulation frequency in support of benign classification;Does not segregate with disease in family study (genes with incomplete penetrance);Other data supporting benign classification
Invitae RCV001081398 SCV000255289 likely benign Hereditary nonpolyposis colon cancer 2019-12-31 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000199450 SCV000296933 uncertain significance Lynch syndrome 2015-10-31 criteria provided, single submitter clinical testing
Counsyl RCV000411225 SCV000488729 uncertain significance Hereditary nonpolyposis colorectal cancer type 4 2016-06-01 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000417397 SCV000601836 benign not specified 2017-05-10 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000515268 SCV000611422 uncertain significance Turcot syndrome; Hereditary nonpolyposis colorectal cancer type 4 2017-05-23 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000034624 SCV000697331 uncertain significance not provided 2016-10-14 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000034624 SCV000806199 uncertain significance not provided 2016-11-22 criteria provided, single submitter clinical testing
GeneKor MSA RCV000115676 SCV000822130 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Mendelics RCV000199450 SCV000838172 uncertain significance Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000199450 SCV000886459 likely benign Lynch syndrome 2018-10-12 criteria provided, single submitter clinical testing The PMS2 variant designated as NM_000059.3:c.2149C>T (p.Val470Met) is classified as likely benign. This variant has been reported at a frequency of 1 in 70 individuals with Ashkenazi Jewish ancestry, and it is present in multiple ethnic populations (gnomad.broadinstitute.org). Variants present at this population frequency are unlikely to be associated with high penetrance hereditary cancer risk. This variant has also been seen in an individual with a co-occurring pathogenic mutation, adding evidence that it is benign. This variant is in ClinVar (Variation ID: 41709) and has been classified as likely benign by other clinical laboratories. Bayesian analysis integrating all of this data (Tavtigian et al, 2018) gives about 1% probability of pathogenicity, which is consistent with a classification of likely benign. This variant is not predicted to alter PMS2 function or modify cancer risk. A modest (less than 2 fold) increase in cancer risk due to this variant cannot be entirely excluded. This analysis was performed in conjunction with the family studies project as part of the University of Washington Find My Variant Study.
Mendelics RCV000411225 SCV001137282 uncertain significance Hereditary nonpolyposis colorectal cancer type 4 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000417397 SCV001157937 likely benign not specified 2018-12-19 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000411225 SCV001324103 uncertain significance Hereditary nonpolyposis colorectal cancer type 4 2018-09-17 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034624 SCV000043416 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000417397 SCV000691961 uncertain significance not specified no assertion criteria provided clinical testing

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