Clinical Domain Working Groups

Kidney Cystic and Ciliopathy Disorders VCEP will focus on cystic kidney disease, with an initial focus on Autosomal Dominant Polycystic Kidney Disease (ADPKD). This group plans to begin with the most common and highly penetrant genes within our area of focus for variant curation and steadily enlarge the scope of the project overtime to encompass a wider range of cystic kidney disease genes, as outlined below.

The Kidney Cystic and Ciliopathy Disorders VCEP aims to specify the existing ACMG guidelines for variant classification in PKD genes and review variants for expert classification including resolving discrepancies in existing variant classification in ClinVar prioritizing the most common genes and variants associated to PKD.

Phase 1: Focus on PKD1

We expect that initial efforts will focus on the key player in autosomal dominant PKD (PKD1) which poses considerable issues surrounding the implementation of the ACMG/AMP guidelines and is responsible for approximately 78% of PKD cases. The establishment of guidelines surrounding pathogenicity assessment of previously reported plus unreported missense variants in PKD1 has been identified as a key goal of the VCEP.

Phase 2: Widen scope to include all autosomal dominant PKD genes

Once guidelines for PKD1 have been established, the expert panel’s expertise will be applied to the wider range of autosomal dominant PKD genes (PKD2, GANAB, ALG9 and DNAJB11) as well as the autosomal recessive PKD (ARPKD) gene, PKHD1.