ClinVar Miner

Submissions for variant NM_025132.4(WDR19):c.781dup (p.Thr261fs) (rs748656635)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000779441 SCV000916061 uncertain significance WDR19-Related Disorders 2018-01-16 criteria provided, single submitter clinical testing 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.
Baylor Genetics RCV000850616 SCV000992849 pathogenic Nephronophthisis 13; Senior-Loken syndrome 8 2017-12-31 criteria provided, single submitter clinical testing
Invitae RCV001231474 SCV001403998 pathogenic Asphyxiating thoracic dystrophy 5; Senior-Loken syndrome 8 2019-08-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr261Asnfs*13) in the WDR19 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individuals affected with asphyxiating thoracic dystrophy (PMID: 28973083, 29068549). ClinVar contains an entry for this variant (Variation ID: 446634). Loss-of-function variants in WDR19 are known to be pathogenic (PMID: 22019273, 23559409, 23683095, 26275793, 27241786, 29068549). For these reasons, this variant has been classified as Pathogenic.
Dan Cohn Lab,University Of California Los Angeles RCV000515920 SCV000612046 pathogenic Jeune thoracic dystrophy 2017-06-01 no assertion criteria provided research
University of Washington Center for Mendelian Genomics, University of Washington RCV000515920 SCV001479399 likely pathogenic Jeune thoracic dystrophy no assertion criteria provided research

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