ClinVar

Description

The WDR19 c.781dupA (p.Thr261AsnfsTer13) frameshift variant has been reported in three studies, where it was found in a compound heterozygous state with a missense variant in one individual and in a heterozygous state in three individuals in whom a second variant was not identified (Halbritter et al. 2013; Coussa et al. 2013; Zhang et al. 2018). The compound heterozygous individual and two of the heterozygous individuals showed features of asphyxiating thoracic dystrophy; one of these heterozygotes also exhibited night blindness and was diagnosed with Senior-Løken syndrome. The third heterozygous individual had isolated nephronophthisis. The p.Thr261AsnfsTer13 variant was absent from at least 192 healthy control subjects and is reported at a frequency of 0.000079 in the European (non-Finnish) population of the Genome Aggregation Database. Functional studies have not been conducted for the p.Thr261AsnfsTer13 variant, which occurs in the fifth WD40 repeat domain of the protein. Due to the limited evidence available and the potential impact of frameshift variants, the p.Thr261AsnfsTer13 variant is classified as a variant of unknown significance but suspicious for pathogenicity for WDR19-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.