Submissions for variant NM_006005.3(WFS1):c.2667G>A (p.Ala889=)

gnomAD frequency: 0.00015  dbSNP: rs71526454

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000152702	SCV000202084	likely benign	not specified	2014-08-19	criteria provided, single submitter	clinical testing	Ala889Ala in exon 8 of WFS1: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and it is not located wi thin the splice consensus sequence. In addition, this variant has been identifi ed in 0.08% (1/1246) of European chromosomes in the ClinSeq project (rs71526454) .
GeneDx	RCV000864405	SCV000515281	likely benign	not provided	2021-01-25	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000864405	SCV001005201	likely benign	not provided	2024-01-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000864405	SCV001249100	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	WFS1: BP4, BP7
Illumina Laboratory Services, Illumina	RCV001156288	SCV001317776	uncertain significance	Autosomal dominant nonsyndromic hearing loss 6	2018-01-13	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	RCV001157955	SCV001319564	uncertain significance	WFS1-Related Spectrum Disorders	2018-01-13	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.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV003128231	SCV003804295	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 rs71526454 in Wolfram's syndrome yet.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000864405	SCV002036810	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000864405	SCV002037618	likely benign	not provided		no assertion criteria provided	clinical testing