Submissions for variant NM_025132.4(WDR19):c.2872G>A (p.Ala958Thr)

gnomAD frequency: 0.00003  dbSNP: rs1057523257

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000417853	SCV000531262	uncertain significance	not provided	2016-08-31	criteria provided, single submitter	clinical testing	The A958T variant in the WDR19 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A958T variant was not observed in approximately 5,900 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A958T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret A958T as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001861610	SCV002252268	uncertain significance	Asphyxiating thoracic dystrophy 5; Senior-Loken syndrome 8	2022-08-10	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 958 of the WDR19 protein (p.Ala958Thr). This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with WDR19-related conditions. ClinVar contains an entry for this variant (Variation ID: 388871). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics	RCV002481324	SCV002790345	uncertain significance	Asphyxiating thoracic dystrophy 5; Nephronophthisis 13; Cranioectodermal dysplasia 4; Senior-Loken syndrome 8; Spermatogenic failure 72	2021-09-07	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002526357	SCV003557028	uncertain significance	Inborn genetic diseases	2021-07-06	criteria provided, single submitter	clinical testing	The c.2872G>A (p.A958T) alteration is located in exon 25 (coding exon 25) of the WDR19 gene. This alteration results from a G to A substitution at nucleotide position 2872, causing the alanine (A) at amino acid position 958 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV004735520	SCV005353145	uncertain significance	WDR19-related disorder	2024-09-16	no assertion criteria provided	clinical testing	The WDR19 c.2872G>A variant is predicted to result in the amino acid substitution p.Ala958Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.021% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.