ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.2327A>T (p.Glu776Val) (rs56002719)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000152695 SCV000202071 benign not specified 2012-05-07 criteria provided, single submitter clinical testing Glu776Val in Exon 08 of WFS1: This variant is not expected to have clinical sign ificance because it has been identified in 0.4% (31/7006) of European American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs56002719).
GeneDx RCV000658991 SCV000252554 uncertain significance not provided 2018-07-19 criteria provided, single submitter clinical testing The E776V variant in the WFS1 gene has been reported previously in association with autosomal recessive Wolfram syndrome in an individual who was compound heterozygous for E776V and a second missense variant in the WFS1 gene (Smith et al., 2004). This variant has also been reported in an individual with non-syndromic hearing loss who did not have a second variant in WFS1 identified by sequencing; however, the E776V variant did not segregate with hearing loss in this family (Häkli et al., 2014). The E776V variant is observed in 270/25788 (1.05%) alleles from individuals of Finnish background, including 2 unrelated homozygous individuals in large population cohorts (Lek et al., 2016). The E776V variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret E776V as a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000351538 SCV000450670 likely benign WFS1-Related Spectrum Disorders 2018-03-06 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000658991 SCV000780794 uncertain significance not provided 2017-12-01 criteria provided, single submitter clinical testing
Personalized Diabetes Medicine Program,University of Maryland School of Medicine RCV000664094 SCV000787546 benign Monogenic diabetes 2017-03-10 criteria provided, single submitter research ACMG Criteria:PP3 (10 predictors), BS1 (1.15% in ExAC Finnish population, 1 homo in ExAC), BS2 (39 cases and 42 controls in type2diabetesgenetics.org)
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000152695 SCV000854880 benign not specified 2017-11-21 criteria provided, single submitter clinical testing
Invitae RCV000658991 SCV001005785 benign not provided 2020-11-26 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001157779 SCV001319381 benign Autosomal dominant nonsyndromic deafness 6 2018-03-06 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001289570 SCV001477527 likely benign none provided 2020-02-28 criteria provided, single submitter clinical testing

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