Submissions for variant NM_006005.3(WFS1):c.2611G>A (p.Val871Met)

gnomAD frequency: 0.00761  dbSNP: rs71532874

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000081342	SCV000113272	benign	not specified	2013-08-09	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000081342	SCV000153535	benign	not specified	2016-01-17	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000081342	SCV000202083	benign	not specified	2012-05-07	criteria provided, single submitter	clinical testing	Val871Met in Exon 08 of WFS1: This variant is not expected to have clinical sign ificance because it has been identified in 1.1% (75/7020) of European American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs71532874).
GeneDx	RCV000421798	SCV000252503	benign	not provided	2019-04-26	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 20981092, 25262649, 12107816, 15605410, 20875904, 25895475, 30245029)
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000081342	SCV000297200	benign	not specified	2015-11-10	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000081342	SCV000311330	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000342228	SCV000450707	benign	Autosomal dominant nonsyndromic hearing loss 6	2018-03-06	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000421798	SCV000511248	benign	not provided	2016-12-30	criteria provided, single submitter	clinical testing
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV000445441	SCV000537023	benign	Monogenic diabetes	2018-12-07	criteria provided, single submitter	research	ACMG criteria: BS2 (16 homozygotes in gnomAD), BS1 (allele frequency is 0.01358 of gnomAD European Finish, which means carrier frequency is 0.0018, above the disease frequency of 1/5000 for WFS)= benign; REVEL 0.255 + PP3/6 predictors + BP4/5 predictors= conflicting evidence, not using
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000421798	SCV000605608	benign	not provided	2023-09-22	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000421798	SCV000844885	benign	not provided	2018-07-30	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000421798	SCV001013354	benign	not provided	2025-01-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001156285	SCV001317773	benign	WFS1-Related Spectrum Disorders	2018-03-06	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002464106	SCV002626370	uncertain significance	Wolfram syndrome 1		criteria provided, single submitter	research	Mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy. rs71532874 variant is also seen in patients with Diabetes Mellitus. However, the role of this particular variant is yet to be ascertained.
Fulgent Genetics, Fulgent Genetics	RCV002498427	SCV002805272	likely benign	Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome	2022-04-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000421798	SCV004011522	likely benign	not provided	2024-10-01	criteria provided, single submitter	clinical testing	WFS1: PM5, BS1, BS2
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000081342	SCV001953102	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000081342	SCV001972770	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000421798	SCV002036980	likely benign	not provided		no assertion criteria provided	clinical testing