ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.9683C>A (p.Ser3228Ter)

dbSNP: rs1057516445
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411250 SCV000485690 likely pathogenic Autosomal recessive polycystic kidney disease 2016-01-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000411250 SCV001361898 likely pathogenic Autosomal recessive polycystic kidney disease 2021-07-11 criteria provided, single submitter clinical testing Variant summary: PKHD1 c.9683C>A (p.Ser3228X) 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 was absent in 251218 control chromosomes. c.9683C>A has been reported in the literature in at-least one compound heterozygote individual affected with Polycystic Kidney Disease (example, Losekoot_2005). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic (n=1)/likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000411250 SCV001587252 pathogenic Autosomal recessive polycystic kidney disease 2020-03-14 criteria provided, single submitter clinical testing Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). This variant has been observed in individual(s) with autosomal recessive polycystic kidney disease (PMID: 16133180). ClinVar contains an entry for this variant (Variation ID: 370381). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser3228*) in the PKHD1 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic.

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