ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.823C>T (p.Gln275Ter) (rs587780062)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115704 SCV000149613 pathogenic not provided 2016-07-01 criteria provided, single submitter clinical testing This pathogenic variant is denoted PMS2 c.823C>T at the cDNA level and p.Gln275Ter (Q275X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA) , and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been observed in at least two families with features of Lynch syndrome (ten Broeke 2015) as well as in a confirmed compound heterozygous state with another PMS2 pathogenic variant in an individual with constitutional mismatch repair deficiency (Yeung 2013) and is considered pathogenic.
Ambry Genetics RCV000216292 SCV000276072 pathogenic Hereditary cancer-predisposing syndrome 2017-08-01 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)
Invitae RCV000552808 SCV000625695 pathogenic Hereditary nonpolyposis colon cancer 2018-12-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln275*) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs587780062, ExAC 0.009%). This variant has been reported in several individuals affected with Lynch syndrome ( PMID: 24689082, 26110232) and in one individual affected with constitutional mismatch repair deficiency (PMID: 23012243). ClinVar contains an entry for this variant (Variation ID: 127796). Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). For these reasons, this variant has been classified as Pathogenic.
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000709755 SCV000840050 pathogenic Hereditary nonpolyposis colorectal cancer type 4 2017-11-26 criteria provided, single submitter clinical testing This c.823C>T (p.Gln275*) variant in the PMS2 gene is predicted to introduce a premature translation termination codon. This variant has been reported in multiple patients with cancer (PMID: 22848017, 25512458, 24689082, 26681312). The c.823C>T (p.Gln275*) variant in the PMS2 gene is classified as pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000763589 SCV000894428 pathogenic Turcot syndrome; Hereditary nonpolyposis colorectal cancer type 4 2018-10-31 criteria provided, single submitter clinical testing
Color RCV000216292 SCV000905475 pathogenic Hereditary cancer-predisposing syndrome 2018-03-22 criteria provided, single submitter clinical testing

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