ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1939A>T (p.Lys647Ter) (rs201451115)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000507921 SCV000604888 pathogenic not specified 2017-06-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000128864 SCV000172720 pathogenic Hereditary cancer-predisposing syndrome 2017-07-11 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)
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000414304 SCV000609841 pathogenic not provided 2017-04-17 criteria provided, single submitter clinical testing
Color RCV000128864 SCV000537649 pathogenic Hereditary cancer-predisposing syndrome 2016-07-30 criteria provided, single submitter clinical testing
GeneDx RCV000414304 SCV000490733 pathogenic not provided 2018-06-21 criteria provided, single submitter clinical testing This pathogenic variant is denoted PMS2 c.1939A>T at the cDNA level and p.Lys647Ter (K647X) at the protein level. The substitution creates a nonsense variant, which changes a Lysine to a premature stop codon (AAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in individuals with early-onset colon cancer with loss of PMS2 protein in their tumors, and in at least one individual with ovarian cancer (Senter 2008, Norquist 2015, Win 2015, Goodenberger 2016, Rosty 2016). Based on the currently available evidence, this variant is considered pathogenic.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000709754 SCV000993577 pathogenic Hereditary nonpolyposis colorectal cancer type 4 2018-07-11 criteria provided, single submitter research
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000709754 SCV000840048 pathogenic Hereditary nonpolyposis colorectal cancer type 4 2017-09-19 criteria provided, single submitter clinical testing This c.1939A>T (p.Lys647*) variant in the PMS2 gene is predicted to is predicted to introduce a premature translation termination codon. This variant has been reported in multiple patients with Lynch syndrome or colorectal cancer (PMID: 18602922, 25856668, 23012243). The c.1939A>T (p.Lys647*) variant in the PMS2 gene is classified as pathogenic.
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076836 SCV000108323 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Invitae RCV000627727 SCV000259395 pathogenic Hereditary nonpolyposis colon cancer 2018-11-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys647*) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs201451115, ExAC 0.001%). This variant has been reported in multiple individuals affected with Lynch syndrome (PMID: 18602922, 25856668, 23012243) and an individual affected with ovarian cancer (PMID: 26720728). Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics RCV000414304 SCV000806192 pathogenic not provided 2017-02-20 criteria provided, single submitter clinical testing

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