ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.943C>T (p.Arg315Ter) (rs200640585)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115711 SCV000212770 pathogenic Hereditary cancer-predisposing syndrome 2017-11-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
CSER_CC_NCGL; University of Washington Medical Center RCV000148734 SCV000190469 pathogenic Colorectal cancer, non-polyposis 2014-06-01 no assertion criteria provided research
Color RCV000115711 SCV000691128 pathogenic Hereditary cancer-predisposing syndrome 2017-08-04 criteria provided, single submitter clinical testing
Counsyl RCV000576503 SCV000677745 pathogenic Hereditary nonpolyposis colorectal cancer type 4 2015-10-02 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763587 SCV000894426 pathogenic Turcot syndrome; Hereditary nonpolyposis colorectal cancer type 4 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000212858 SCV000149620 pathogenic not provided 2018-06-04 criteria provided, single submitter clinical testing This pathogenic variant is denoted PMS2 c.943C>T at the cDNA level and p.Arg315Ter (R315X) at the protein level. The substitution creates a nonsense variant, changing an Arginine to a premature stop codon (CGA>TGA). This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in association with colorectal cancer with immunohistochemical tumor testing showing absent PMS2 expression (Vaughn 2010, Borras 2013, Shia 2013, Goodenberger 2016, Sugano 2016). Based on currently available evidence, we consider this variant to be pathogenic.
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076901 SCV000108398 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Invitae RCV000524484 SCV000261298 pathogenic Hereditary nonpolyposis colon cancer 2018-12-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg315*) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs200640585, ExAC 0.01%). This variant has been reported in individuals affected with Lynch syndrome and colon cancer (PMID: 20205264, 23709753, 22918162, 25856668, 27589204). ClinVar contains an entry for this variant (Variation ID: 91382) Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212858 SCV000888422 pathogenic not provided 2017-11-07 criteria provided, single submitter clinical testing

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