The PKD2 gene has been associated with autosomal dominant polycystic kidney disease in over 15 probands in 6 curated publications. PKD2 was first associated with this disease in humans in 1996 (Mochizuki et al.). Variants in this gene segregate with disease and can occur de novo. The mechanism for disease is known to be loss of function. 53 unique variants (missense, in-frame indel, nonsense, frameshift, large deletion and complex rearrangements) have been classified as Pathogenic in ClinVar, 30 of which are frameshift, nonsense or canonical splice changes. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. This gene-disease association is supported by ample experimental evidence including expression studies, biochemical function, protein interactions and animal models that recapitulate the human disease. Evidence to support a biallelic PKD2 phenotype in humans has been reviewed, but there is currently insufficient literature available to support an autosomal recessive gene-disease relationship (PMIDs: 22114106, 33168999). In summary, PKD2 is definitively associated with autosomal dominant polycystic kidney disease. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen General Gene Curation Working Group on 5/22/2019 (SOP Version 6).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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