Submissions for variant NM_025132.4(WDR19):c.2608G>A (p.Asp870Asn)

gnomAD frequency: 0.00064  dbSNP: rs201963605

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000486591	SCV000573089	uncertain significance	not provided	2020-09-18	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31844813)
Invitae	RCV001078579	SCV001091607	likely benign	Asphyxiating thoracic dystrophy 5; Senior-Loken syndrome 8	2024-01-18	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000486591	SCV001159724	uncertain significance	not provided	2020-01-13	criteria provided, single submitter	clinical testing	The WDR19 c.2608G>A; p.Asp870Asn variant (rs201963605) has not been reported in association with a skeletal dysplasia, but is reported in the homozygous state in two siblings with a ciliopathy suggestive of Meckel Gruber syndrome (Al Alawi 2019). This variant is reported in ClinVar (Variation ID: 423393), and is found in the South Asian population with an overall allele frequency of 0.29% (88/30600 alleles) in the Genome Aggregation Database. The aspartate at codon 870 is highly conserved, but computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Given the lack of clinical and functional data, the significance of the p.Asp870Asn variant is uncertain at this time. References: Al Alawi I et al. Molecular Genetic Diagnosis of Omani Patients With Inherited Cystic Kidney Disease. Kidney Int Rep. 2019 Aug 30;4(12):1751-1759.
Illumina Laboratory Services, Illumina	RCV001146437	SCV001307181	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	RCV001146438	SCV001307182	likely benign	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Genetic Services Laboratory, University of Chicago	RCV001821402	SCV002064872	uncertain significance	not specified	2018-02-28	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004535530	SCV004720010	likely benign	WDR19-related disorder	2023-09-11	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).