ClinVar Miner

Submissions for variant NM_000553.6(WRN):c.2665C>T (p.Arg889Ter)

gnomAD frequency: 0.00002  dbSNP: rs774765029
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000456191 SCV000541469 pathogenic Werner syndrome 2024-01-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg889*) in the WRN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WRN are known to be pathogenic (PMID: 16673358). This variant is present in population databases (rs774765029, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with Werner syndrome (PMID: 8968742, 9012406, 16673358, 16786514). ClinVar contains an entry for this variant (Variation ID: 404045). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000456191 SCV004208810 pathogenic Werner syndrome 2023-09-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000456191 SCV004241254 pathogenic Werner syndrome 2023-12-18 criteria provided, single submitter clinical testing Variant summary: WRN c.2665C>T (p.Arg889X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2.4e-05 in 251074 control chromosomes. c.2665C>T has been reported in the literature in multiple individuals affected with Werner Syndrome (eg. Huang_2006). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV001580038 SCV001809447 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001580038 SCV001966582 pathogenic not provided no assertion criteria provided clinical testing

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