Submissions for variant NM_006005.3(WFS1):c.1675G>A (p.Ala559Thr)

gnomAD frequency: 0.00396  dbSNP: rs55814513

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000150097	SCV000113263	benign	not specified	2013-11-20	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000150097	SCV000153525	likely benign	not specified	2018-08-06	criteria provided, single submitter	clinical testing
GeneDx	RCV000150097	SCV000169822	benign	not specified	2014-04-14	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000150097	SCV000202046	benign	not specified	2016-06-09	criteria provided, single submitter	clinical testing	p.Ala559Thr in Exon 08 of WFS1: This variant is not expected to have clinical si gnificance because it has been identified in 0.6% (416/66596) European chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; r s55814513).
Illumina Laboratory Services, Illumina	RCV000281797	SCV000450626	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	RCV000336857	SCV000450627	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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000081339	SCV000605613	benign	not provided	2023-11-24	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000081339	SCV000609133	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	WFS1: PM5, BS2
Invitae	RCV000081339	SCV001005235	benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000081339	SCV001146650	likely benign	not provided	2018-11-27	criteria provided, single submitter	clinical testing
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV001174423	SCV001337561	benign	Monogenic diabetes	2019-01-11	criteria provided, single submitter	research	ACMG criteria: BS2 (71 cases and 81 controls in type2diabetesgenetics.org) + BS1 (0.6 MAF in gnomAD European and ENF) = benign (REVEL 0.407 + PP3/3 predictors + BP4/6 predictors = conflicting evidence, not using)
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002464105	SCV002640383	likely benign	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. rs55814513 variant is also seen in patients with Diabetes Mellitus. However, the role of this particular variant is yet to be ascertained.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000081339	SCV001798767	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000081339	SCV001924949	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000081339	SCV001951663	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000081339	SCV001965670	likely benign	not provided		no assertion criteria provided	clinical testing