ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.2254G>T (p.Glu752Ter)

gnomAD frequency: 0.00002  dbSNP: rs201239579
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000195490 SCV000252542 pathogenic not provided 2024-02-06 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 15277431, 15852062, 34789499, 28432734, 26025012, 23981289, 36208030, 37508961, 10521293)
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota RCV001730586 SCV001981523 likely pathogenic Wolfram-like syndrome 2021-08-25 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000195490 SCV002065919 likely pathogenic not provided 2022-01-20 criteria provided, single submitter clinical testing DNA sequence analysis of the WFS1 gene demonstrated a sequence change,c.2254G>T , which results in the creation of a premature stop codon at amino acid position 752, p.Glu752*. This pathogenic sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated WFS1 protein with potentially abnormal function. This sequence change has been described in the gnomAD database in one heterozygous individual which corresponds to a population frequency of 0.00041% (dbSNP rs201239579). This sequence change has been reported previously in two individuals with Wolfram syndrome (PMID: 10521293). In one individual, a frameshift variant and a missense variant were also identified in the WFS1 gene, while in the second individual no other variants in WFS1 were identified (PMID: 10521293).
Labcorp Genetics (formerly Invitae), Labcorp RCV000195490 SCV003525499 pathogenic not provided 2024-04-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu752*) in the WFS1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 139 amino acid(s) of the WFS1 protein. This variant is present in population databases (rs201239579, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with Wolfram syndrome (PMID: 15277431, 23981289). ClinVar contains an entry for this variant (Variation ID: 215399). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005031741 SCV005667550 pathogenic Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2024-04-30 criteria provided, single submitter clinical testing

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