ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.8011C>T (p.Arg2671Ter) (rs137852947)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000004328 SCV000942874 pathogenic Autosomal recessive polycystic kidney disease 2018-09-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2671*) in the PKHD1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs137852947, ExAC 0.03%). This variant has been observed in several individuals affected with PKHD1-related conditions (PMID: 11919560, 28364132, 26695994, 27225849). ClinVar contains an entry for this variant (Variation ID: 4112). Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000004328 SCV001163030 pathogenic Autosomal recessive polycystic kidney disease criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000004328 SCV001338100 pathogenic Autosomal recessive polycystic kidney disease 2020-01-20 criteria provided, single submitter clinical testing Variant summary: PKHD1 c.8011C>T (p.Arg2671X) 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 3.6e-05 in 251182 control chromosomes (gnomAD). c.8011C>T has been reported in the literature in multiple individuals affected with Polycystic Kidney and Hepatic Disease (e.g. Ward_2002, Obeidova_2015, Melchionda_2016). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000004328 SCV000024499 pathogenic Autosomal recessive polycystic kidney disease 2002-03-01 no assertion criteria provided literature only

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