ClinVar

Description

The p.Thr261AsnfsX13 variant in WDR19 has been reported in the compound heterozygous state with another WDR19 variant in at least 2 individuals with clinical features of WDR19-associated ciliopathies (including asphyxiating thoracic dystrophy and/or nephronophthisis). It was also reported in the heterozygous state in 3 individuals with clinical features consistent with WDR-19 associated ciliopathies where a second variant was not identified (Halbritter 2013 PMID: 23559409, Coussa 2013 PMID: 23683095, Meng 2017 PMID: 28973083, Zhang 2018 PMID: 29068549, Liu 2019 PMID: 31216405). This variant has been reported by other clinical laboratories in ClinVar (Variation ID 446634) and has been identified in 0.007% (3/41448) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org, v.3.1.2), at a frequency low enough to be consistent with a recessive carrier frequency. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 261 and leads to a premature termination codon 13 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function variants in WDR19 gene have been reported in individuals with autosomal recessive ciliopathies (Bredrup 2011 PMID: 22019273, Zhang 2018 PMID: 29068549). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive WDR19-associated ciliopathies. ACMG/AMP Criteria applied: PVS1, PM3, PM2_Supporting.