ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.817G>T (p.Glu273Ter)

dbSNP: rs142428158
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001875777 SCV002237677 pathogenic not provided 2024-10-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu273*) in the WFS1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 618 amino acid(s) of the WFS1 protein. This variant is present in population databases (rs142428158, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with Wolfram syndrome (PMID: 10521293, 23981289). ClinVar contains an entry for this variant (Variation ID: 918066). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002497609 SCV002810296 pathogenic Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2021-10-08 criteria provided, single submitter clinical testing
Constantin Polychronakos Laboratory, The Research Institute of the McGill University Health Centre RCV001175321 SCV001250636 pathogenic Diabetes mellitus no assertion criteria provided research PVS1 PS1 PM2 PP3
PreventionGenetics, part of Exact Sciences RCV004738178 SCV005362491 pathogenic WFS1-related disorder 2024-09-12 no assertion criteria provided clinical testing The WFS1 c.817G>T variant is predicted to result in premature protein termination (p.Glu273*). This variant has been reported as pathogenic in three patients with autosomal recessive Wolfram syndrome (Hardy et al. 1999. PubMed ID: 10521293; Marshall et al. 2013. PubMed ID: 23981289) and has also been reported in the heterozygous state in a patient with type 1 diabetes (Marchand et al. 2021. PubMed ID: 33538814). This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Nonsense variants in WFS1 are expected to be pathogenic. This variant is interpreted as pathogenic.

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