Submissions for variant NM_006005.3(WFS1):c.1277G>A (p.Cys426Tyr)

gnomAD frequency: 0.00160  dbSNP: rs35218685

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038636	SCV000062314	benign	not specified	2017-07-05	criteria provided, single submitter	clinical testing	p.Cys426Tyr in exon 8 of WFS1: This variant is not expected to have clinical sig nificance because it is has been identified in 5% (511/10150 Ashkenazi Jewish ch romosomes including 10 homozygotes by the genome Aggregation Database (gnomAD, h ttp://gnomad.broadinstitute.org; dbSNP rs35218685).
Genetic Services Laboratory, University of Chicago	RCV000038636	SCV000153518	likely benign	not specified	2015-06-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000038636	SCV000169818	benign	not specified	2014-04-24	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756927	SCV000884914	benign	not provided	2021-10-21	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000756927	SCV001013011	benign	not provided	2025-01-20	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001157341	SCV001318903	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). 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.
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV001174420	SCV001337558	likely benign	Monogenic diabetes	2018-01-12	criteria provided, single submitter	research	ACMG criteria: PP3 (4 predictors), BP4 (5 predictors), BS2 (36 cases and 42 controls in type2diabetesgenetics.org), BP6 (GeneDx says benign and Partners and Chicago call likely benign)=likely benign
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002464095	SCV002619480	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. rs35218685 variant is also seen in patients with Diabetes Mellitus. However, the role of this particular variant is yet to be ascertained.
CeGaT Center for Human Genetics Tuebingen	RCV000756927	SCV004185214	likely benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	WFS1: BS2
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000756927	SCV002035439	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000756927	SCV002037620	likely benign	not provided		no assertion criteria provided	clinical testing