Submissions for variant NM_006005.3(WFS1):c.1758C>T (p.Ala586=)

gnomAD frequency: 0.00021  dbSNP: rs145144527

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155345	SCV000205031	likely benign	not specified	2016-01-29	criteria provided, single submitter	clinical testing	p.Ala586Ala in Exon 08 of WFS1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 41/66666 European ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; dbSNP rs145144527).
Illumina Laboratory Services, Illumina	RCV000272593	SCV000450634	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	RCV000327617	SCV000450635	likely benign	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV001704130	SCV000515274	likely benign	not provided	2019-09-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001704130	SCV002371307	benign	not provided	2024-01-24	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV003126556	SCV003801411	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 rs145144527 in Wolfram's syndrome yet.
CeGaT Center for Human Genetics Tuebingen	RCV001704130	SCV004147642	likely benign	not provided	2022-12-01	criteria provided, single submitter	clinical testing	WFS1: BP4, BP7
Clinical Genetics, Academic Medical Center	RCV000155345	SCV001926108	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001704130	SCV001973870	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001704130	SCV002036335	likely benign	not provided		no assertion criteria provided	clinical testing