Submissions for variant NM_025132.4(WDR19):c.3667C>T (p.Arg1223Cys)

gnomAD frequency: 0.00150  dbSNP: rs201597047

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000385239	SCV000449434	uncertain significance	Asphyxiating thoracic dystrophy 5	2018-01-13	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	RCV000288576	SCV000449435	uncertain significance	Cranioectodermal dysplasia 4	2018-01-13	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.
CeGaT Center for Human Genetics Tuebingen	RCV000488404	SCV000575408	uncertain significance	not provided	2016-10-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000488404	SCV000884899	uncertain significance	not provided	2023-10-09	criteria provided, single submitter	clinical testing	The WDR19 c.3667C>T; p.Arg1223Cys variant (rs201597047), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 348754). This variant is found in the general population with an overall allele frequency of 0.16% (447/280632 alleles, including 3 homozygotes) in the Genome Aggregation Database. The arginine at position 1223 is moderately conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.750). Due to limited information, the clinical significance of this variant is uncertain at this time.
Invitae	RCV001083150	SCV001096889	likely benign	Asphyxiating thoracic dystrophy 5; Senior-Loken syndrome 8	2024-01-25	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004530412	SCV004711246	benign	WDR19-related disorder	2019-08-07	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).