Submissions for variant NM_006005.3(WFS1):c.917T>C (p.Met306Thr)

gnomAD frequency: 0.00389  dbSNP: rs146114074

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000154149	SCV000203815	benign	not specified	2014-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000312681	SCV000450592	benign	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000355811	SCV000450593	benign	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000154149	SCV000515269	benign	not specified	2015-06-10	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	RCV000154149	SCV000711247	benign	not specified	2012-04-30	criteria provided, single submitter	clinical testing	Met306Thr in Exon 08 of WFS1: This variant is not expected to have clinical sign ificance because it has been identified in 1.2% (45/3738) of African American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS; dbSNP rs146114074).
Invitae	RCV000870981	SCV001012565	benign	not provided	2024-01-22	criteria provided, single submitter	clinical testing
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV001174388	SCV001337526	benign	Monogenic diabetes	2018-05-18	criteria provided, single submitter	research	ACMG criteria: BP4 (8 predictors, Revel score 0.141; 2 predictors for PP3, not using), BS1 (1.4% in 1000G African, 1.3% in gnomAD African), BS2 (37 cases and 31 controls in type2diabetesgenetics.org; 3 homozygotes in gnomAD African)= benign
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000870981	SCV001473982	benign	not provided	2023-09-15	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002464008	SCV002605282	uncertain significance	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 rs146114074 yet.
Clinical Genetics, Academic Medical Center	RCV000154149	SCV002034426	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000870981	SCV002036527	likely benign	not provided		no assertion criteria provided	clinical testing