ClinVar Miner

Submissions for variant NM_007055.4(POLR3A):c.2617-1G>A

gnomAD frequency: 0.00002  dbSNP: rs181087667
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000384524 SCV000329966 pathogenic not provided 2022-05-25 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Canonical splice site variant predicted to result in abnormal splicing; This variant is associated with the following publications: (PMID: 25339210, 21855841, 30414627, 30323018, 28459997)
Tartaglia Lab, Genetics and Rare Diseases Research Division,Bambino Gesu' Children's Hospital RCV000754391 SCV000786642 likely pathogenic Neonatal pseudo-hydrocephalic progeroid syndrome 2018-05-01 criteria provided, single submitter research
Cole/Wambach Lab,Washington University in St. Louis RCV000754391 SCV000886479 pathogenic Neonatal pseudo-hydrocephalic progeroid syndrome 2018-10-01 criteria provided, single submitter research
CeGaT Center for Human Genetics Tuebingen RCV000384524 SCV001247295 pathogenic not provided 2019-05-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000384524 SCV001447333 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Invitae RCV000384524 SCV002229774 pathogenic not provided 2021-09-18 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 19 of the POLR3A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in POLR3A are known to be pathogenic (PMID: 21855841, 25339210, 27612211, 30414627, 30450527). This variant is present in population databases (rs181087667, ExAC 0.003%). Disruption of this splice site has been observed in individuals with POLR3A-related conditions (PMID: 21855841). This variant is also known as c.2711-1G>A. ClinVar contains an entry for this variant (Variation ID: 31146). 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.
OMIM RCV000024142 SCV000045433 pathogenic Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome 2011-09-09 no assertion criteria provided literature only
GeneReviews RCV000024142 SCV000055887 pathogenic Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome 2017-05-11 no assertion criteria provided literature only
University of Washington Center for Mendelian Genomics, University of Washington RCV000754391 SCV001479502 likely pathogenic Neonatal pseudo-hydrocephalic progeroid syndrome no assertion criteria provided research
OMIM RCV000754391 SCV002520607 pathogenic Neonatal pseudo-hydrocephalic progeroid syndrome 2011-09-09 no assertion criteria provided literature only

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