Submissions for variant NM_006005.3(WFS1):c.2424C>T (p.Ser808=)

gnomAD frequency: 0.00048  dbSNP: rs56035336

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000194535	SCV000249464	uncertain significance	not specified	2015-06-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000327535	SCV000450681	uncertain significance	WFS1-Related Spectrum Disorders	2018-01-12	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000386848	SCV000450682	uncertain significance	Autosomal dominant nonsyndromic hearing loss 6	2018-01-12	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000194535	SCV000515278	benign	not specified	2015-05-20	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)	RCV000727290	SCV000707294	uncertain significance	not provided	2017-04-04	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000194535	SCV000711256	likely benign	not specified	2017-03-07	criteria provided, single submitter	clinical testing	p.Ser808Ser in exon 8 of WFS1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in several populations b y the Genome Aggregation Database, including 69/124924 European chromosomes and 27/34324 Latino chromosomes (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs5 6035336).
Invitae	RCV000727290	SCV001012909	likely benign	not provided	2024-01-26	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV003128234	SCV003804300	benign	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 rs56035336 in Wolfram's syndrome yet.
CeGaT Center for Human Genetics Tuebingen	RCV000727290	SCV004147648	likely benign	not provided	2023-05-01	criteria provided, single submitter	clinical testing	WFS1: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003917779	SCV004731345	likely benign	WFS1-related condition	2019-03-13	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).