ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1909C>T (p.Gln637Ter) (rs1554297125)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000590029 SCV000697311 likely pathogenic Lynch syndrome 2016-04-13 criteria provided, single submitter clinical testing Variant summary: Variant affects a non-conserved nucleotide and results in a nonsense mutation predicted to cause a loss of normal protein function due to production of a truncated protein or by the absence of the protein product due to nonsense-mediated mRNA decay. It is absent from the large and broad cohorts of the ExAC project and to our knowledge, it was not reported in affected individuals either. Loss of function of PMS2 is a known mechanism of Lynch syndrome (GeneReviews), therefore, this nonsense variant was classified as Likely Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759915 SCV000889612 likely pathogenic not provided 2018-01-12 criteria provided, single submitter clinical testing
Invitae RCV001219508 SCV001391451 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-08-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln637*) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 496033). Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). For these reasons, this variant has been classified as Pathogenic.

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