ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.8824C>T (p.Arg2942Ter) (rs398124500)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169555 SCV000221047 likely pathogenic Autosomal recessive polycystic kidney disease 2015-01-16 criteria provided, single submitter literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000790758 SCV000231408 pathogenic not provided 2012-08-30 criteria provided, single submitter clinical testing
Invitae RCV000169555 SCV001211244 pathogenic Autosomal recessive polycystic kidney disease 2019-03-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2942*) in the PKHD1 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 been observed in an individual affected with polycystic kidney disease (PMID: 19940839). ClinVar contains an entry for this variant (Variation ID: 96439). Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). For these reasons, this variant has been classified as Pathogenic.
Victorian Clinical Genetics Services,Murdoch Childrens Research Institute RCV000169555 SCV001427136 pathogenic Autosomal recessive polycystic kidney disease 2018-11-23 criteria provided, single submitter clinical testing A heterozygous nonsense variant, NM_138694.3(PKHD1):c.8824C>T, has been identified in exon 57 of 67 of the PKHD1 gene. The variant is predicted to result in a premature stop codon at position 2942 of the protein (NP_619639.3(PKHD1):p.(Arg2942*)). This variant is predicted to result in loss of protein function through nonsense mediated decay, which is a reported mechanism of pathogenicity for this gene. The variant is present in the gnomAD database at a frequency of 0.0007% (2 heterozygotes, 0 homozygotes). It has been previously described as pathogenic in patients with Polycystic kidney disease (ClinVar, Denamur, E et al (2010)). And many other pathogenic LoF variants in the region have also been reported (ClinVar). Based on the information available at the time of curation, this variant has been classified as PATHOGENIC.

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