ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.8114del (p.Gly2705fs)

dbSNP: rs774050795
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001091107 SCV001246963 pathogenic not provided 2017-04-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001209147 SCV001380570 pathogenic Autosomal recessive polycystic kidney disease 2023-12-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly2705Valfs*11) in the PKHD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). This variant is present in population databases (rs774050795, gnomAD 0.002%). This premature translational stop signal has been observed in individuals with autosomal recessive polycystic kidney disease (PMID: 15805161, 20413436). ClinVar contains an entry for this variant (Variation ID: 871259). 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.
Laboratory of Molecular Genetics, Children's Memorial Health Institute RCV001209147 SCV001434252 pathogenic Autosomal recessive polycystic kidney disease 2020-09-25 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001209147 SCV002041826 pathogenic Autosomal recessive polycystic kidney disease 2021-11-01 criteria provided, single submitter clinical testing Variant summary: PKHD1 c.8114delG (p.Gly2705ValfsX11) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 251160 control chromosomes (gnomAD). c.8114delG has been reported in the literature in multiple individuals affected with Polycystic Kidney And Hepatic Disease (examples: Sharp_2005, Gunay-Aygun_2009, Obeidova_2015, Tong_2016, and Wicher_2020). These data indicate that the variant is associated with disease. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV003462636 SCV004204715 pathogenic Polycystic kidney disease 4 2024-02-14 criteria provided, single submitter clinical testing
Natera, Inc. RCV001209147 SCV002077996 pathogenic Autosomal recessive polycystic kidney disease 2018-10-03 no assertion criteria provided clinical testing

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