Submissions for variant NM_025132.4(WDR19):c.817A>G (p.Asn273Asp)

gnomAD frequency: 0.00004  dbSNP: rs375644378

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001204687	SCV001375904	uncertain significance	Asphyxiating thoracic dystrophy 5; Senior-Loken syndrome 8	2022-08-09	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 273 of the WDR19 protein (p.Asn273Asp). This variant is present in population databases (rs375644378, gnomAD 0.004%). This missense change has been observed in individuals with asphyxiating thoracic dystrophy (PMID: 29068549). ClinVar contains an entry for this variant (Variation ID: 446633). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Fulgent Genetics, Fulgent Genetics	RCV002476032	SCV002791579	pathogenic	Asphyxiating thoracic dystrophy 5; Nephronophthisis 13; Cranioectodermal dysplasia 4; Senior-Loken syndrome 8; Spermatogenic failure 72	2024-05-11	criteria provided, single submitter	clinical testing
Dan Cohn Lab, University Of California Los Angeles	RCV000515807	SCV000612045	pathogenic	Jeune thoracic dystrophy	2017-06-01	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV000515807	SCV001479441	likely pathogenic	Jeune thoracic dystrophy		no assertion criteria provided	research