Submissions for variant NM_025132.4(WDR19):c.2909C>T (p.Ala970Val)

gnomAD frequency: 0.00001  dbSNP: rs771583357

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV001376245	SCV001573319	uncertain significance	Senior-Loken syndrome 8	2021-04-08	criteria provided, single submitter	research	The WDR19 c.2909C>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2, PP3. Based on this evidence we have classified this variant as Variant of Uncertain Significance.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001376245	SCV005045239	uncertain significance	Senior-Loken syndrome 8	2024-05-17	criteria provided, single submitter	curation	The heterozygous p.Ala970Val variant in WDR19 was identified by our study, in the compound heterozygous state, along with a VUS, in one individual with Senior-Loken syndrome 8. However, the phase of these variants are unknown at this time. The variant has been identified in 0.002% (2/68024) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP (rs771583357)). Although this variant has been seen in the general population in a heterozygous state, its frequency is not high enough to rule out a pathogenic role. This variant has been reported in ClinVar (Variation ID: 1065667) and has been interpreted as uncertain significance by Ocular Genomics Institute, Massachusetts Eye and Ear. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Ala970Val variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PP3_Moderate (Richards 2015).