Submissions for variant NM_006005.3(WFS1):c.799G>A (p.Asp267Asn)

gnomAD frequency: 0.00031  dbSNP: rs145677667

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000152667	SCV000202026	uncertain significance	not specified	2013-11-03	criteria provided, single submitter	clinical testing	The Asp267Asn variant in WFS1 has not been reported in individuals with hearing loss, but has been identified in 0.07% (6/8600) of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs145677667). Although this variant has been seen in the general population, it s frequency is not high enough to rule out a pathogenic role. Computational ana lyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, an d SIFT) do not provide strong support for or against an impact to the protein. I n summary, additional data is needed to determine the clinical significance of t his variant.
GeneDx	RCV000767003	SCV000252478	uncertain significance	not provided	2024-12-04	criteria provided, single submitter	clinical testing	Observed in a patient with Wolfram syndrome who harbored a second variant in the WFS1 gene (PMID: 26969326); Identified in an individual with vision loss; a second variant in WFS1 was not identified (PMID: 32483926); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29529044, 34426522, 33841295, 26969326, 32483926, 34515852)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000767003	SCV001542964	likely benign	not provided	2025-01-06	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000767003	SCV001962558	uncertain significance	not provided	2021-09-01	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000767003	SCV004226968	uncertain significance	not provided	2022-08-14	criteria provided, single submitter	clinical testing	PM2_supporting
Fulgent Genetics, Fulgent Genetics	RCV005031660	SCV005664704	uncertain significance	Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome	2024-03-22	criteria provided, single submitter	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000767003	SCV001800308	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000767003	SCV001952960	uncertain significance	not provided		no assertion criteria provided	clinical testing