Submissions for variant NM_025132.4(WDR19):c.929A>G (p.Tyr310Cys)

gnomAD frequency: 0.00030  dbSNP: rs199783864

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000387750	SCV000449368	uncertain significance	Asphyxiating thoracic dystrophy 5	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000274582	SCV000449369	uncertain significance	Cranioectodermal dysplasia 4	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000693524	SCV000821396	uncertain significance	Asphyxiating thoracic dystrophy 5; Senior-Loken syndrome 8	2024-01-14	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 310 of the WDR19 protein (p.Tyr310Cys). This variant is present in population databases (rs199783864, gnomAD 0.05%). 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: 348727). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on WDR19 protein function. 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001002087	SCV001159931	uncertain significance	not specified	2018-09-26	criteria provided, single submitter	clinical testing	The WDR19 variant (rs199783864), to our knowledge, is not described in the medical literature but contains an entry in ClinVar (Variation ID: 348727). It is observed in the general population at an overall frequency of 0.03% (83/267358 alleles) in the Genome Aggregation Database. The tyrosine at codon 310 is moderately conserved, but computational algorithms (PolyPhen-2, SIFT) predict that this variant is tolerated. Due to the lack of clinical and functional data regarding this variant, its clinical significance cannot be determined with certainty.
Fulgent Genetics, Fulgent Genetics	RCV002487533	SCV002786500	uncertain significance	Asphyxiating thoracic dystrophy 5; Nephronophthisis 13; Cranioectodermal dysplasia 4; Senior-Loken syndrome 8; Spermatogenic failure 72	2022-02-11	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002520239	SCV003691373	uncertain significance	Inborn genetic diseases	2022-10-26	criteria provided, single submitter	clinical testing	The c.929A>G (p.Y310C) alteration is located in exon 10 (coding exon 10) of the WDR19 gene. This alteration results from a A to G substitution at nucleotide position 929, causing the tyrosine (Y) at amino acid position 310 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.