Submissions for variant NM_006005.3(WFS1):c.2335G>A (p.Val779Met)

gnomAD frequency: 0.00672  dbSNP: rs141328044

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038657	SCV000062335	benign	not specified	2012-04-30	criteria provided, single submitter	clinical testing	Val779Met in Exon 08 of WFS1: This variant is not expected to have clinical sign ificance because it has been identified in 2.5% (92/3730) of African American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS; dbSNP rs141328044).
GeneDx	RCV000038657	SCV000252500	benign	not specified	2014-06-23	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Eurofins Ntd Llc (ga)	RCV000038657	SCV000341012	benign	not specified	2016-05-26	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000404342	SCV000450671	likely benign	WFS1-Related Spectrum Disorders	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000300529	SCV000450672	likely benign	Autosomal dominant nonsyndromic hearing loss 6	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000515097	SCV000610765	likely benign	not provided	2017-05-15	criteria provided, single submitter	clinical testing
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV000664095	SCV000787547	benign	Monogenic diabetes	2018-09-07	criteria provided, single submitter	research	ACMG criteria: BA1 (2.2% in gnomAD Africans), BS2 (72 cases and 71 controls in T2DM genes) (REVEL 0.696 + PP3/7 predictors + BP4/2 predictors= conflicting evidence, not using); Note: papers associate variant with LFHL (PMID: 11709537, 12955714)=benign
Invitae	RCV000515097	SCV001012011	benign	not provided	2024-01-25	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000515097	SCV002506004	benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002464005	SCV002605296	uncertain risk allele	Wolfram syndrome 1		criteria provided, single submitter	research	Potent mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy.However no sufficient evidence is found to ascertain the role of this particular variant rs141328044 yet.
Fulgent Genetics, Fulgent Genetics	RCV002496613	SCV002810087	likely benign	Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome	2022-04-25	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000038657	SCV001921627	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000038657	SCV001969270	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000515097	SCV002036152	likely benign	not provided		no assertion criteria provided	clinical testing