ClinVar Miner

Submissions for variant NM_007055.4(POLR3A):c.2005C>T (p.Arg669Ter) (rs774007232)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cole/Wambach Lab,Washington University in St. Louis RCV000755668 SCV000886475 pathogenic Neonatal pseudo-hydrocephalic progeroid syndrome 2018-10-01 criteria provided, single submitter research
GeneDx RCV000760689 SCV000890581 pathogenic not provided 2018-08-20 criteria provided, single submitter clinical testing The R669X nonsense variant in the POLR3A gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, the R669X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret R669X as a pathogenic variant.
Invitae RCV000760689 SCV001397179 pathogenic not provided 2019-05-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg669*) in the POLR3A gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs774007232, ExAC 0.01%). This variant has been observed in an individual affected with clinical features of Wiedemann-Rautenstrauch Syndrome (PMID: 30414627). ClinVar contains an entry for this variant (Variation ID: 617891). Loss-of-function variants in POLR3A are known to be pathogenic (PMID: 21855841, 25339210). For these reasons, this variant has been classified as Pathogenic.
Kasturba Medical College, Manipal University RCV000755668 SCV001478355 pathogenic Neonatal pseudo-hydrocephalic progeroid syndrome 2019-05-12 criteria provided, single submitter clinical testing
OMIM RCV000755668 SCV000883070 pathogenic Neonatal pseudo-hydrocephalic progeroid syndrome 2019-02-13 no assertion criteria provided literature only
University of Washington Center for Mendelian Genomics, University of Washington RCV000755668 SCV001479498 likely pathogenic Neonatal pseudo-hydrocephalic progeroid syndrome no assertion criteria provided research

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