Submissions for variant NM_006005.3(WFS1):c.2452C>T (p.Arg818Cys)

gnomAD frequency: 0.00390  dbSNP: rs35932623

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000118865	SCV000153520	benign	not specified	2013-03-27	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000118865	SCV000205099	benign	not specified	2015-04-16	criteria provided, single submitter	clinical testing	p.Arg818Cys in exon 8 of WFS1: This variant is not expected to have clinical sig nificance because it has been identified in 0.8% (129/15874) of South Asian chro mosomes including 1 homozygote by the Exome Aggregation Consortium (ExAC, http:/ /exac.broadinstitute.org; dbSNP rs35932623).
GeneDx	RCV000487646	SCV000252544	benign	not provided	2019-02-01	criteria provided, single submitter	clinical testing	Incidentally identified in the diabetic father of a proband with Wolfram syndrome, though the proband had not inherited this variant (Smith et al., 2004).; Identified in the heterozygous state in another individual who was also homozygous for an in-frame insertion of three amino acids in the WFS1 gene (Smith et al., 2004).; Reported on both WFS1 alleles in an individual with Wolfram syndrome (Domenech et al., 2004); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27151922, 11161832, 11317350, 23595122, 12605098, 23429432, 15277431, 27013921, 11244483, 28432734, 15151504, 29511501, 30245029, 29563951, 31638168)
PreventionGenetics, part of Exact Sciences	RCV000118865	SCV000311327	likely benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000118865	SCV000331434	likely benign	not specified	2015-12-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000336052	SCV000450687	likely benign	WFS1-Related Spectrum Disorders	2017-04-27	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	RCV000403034	SCV000450688	likely benign	Autosomal dominant nonsyndromic hearing loss 6	2017-04-27	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.
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV000445373	SCV000537022	uncertain significance	Monogenic diabetes	2015-07-31	criteria provided, single submitter	research	ACMG Criteria: PP3, PP5 (PMID:21446023), BS2, BP6
CeGaT Center for Human Genetics Tuebingen	RCV000487646	SCV000575400	benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	WFS1: BS1, BS2
Invitae	RCV000487646	SCV001005999	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Mendelics	RCV000987413	SCV001136703	benign	Wolfram syndrome 1	2019-05-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000487646	SCV001158286	likely benign	not provided	2023-09-04	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000487646	SCV004226970	uncertain significance	not provided	2022-05-31	criteria provided, single submitter	clinical testing	BA1, BS1, PP3
Clinical Genetics, Academic Medical Center	RCV000487646	SCV001918899	likely benign	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000487646	SCV001963324	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000487646	SCV002035676	likely benign	not provided		no assertion criteria provided	clinical testing