ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.824C>G (p.Ala275Gly)

gnomAD frequency: 0.00006  dbSNP: rs769151204
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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 RCV001884628 SCV002161769 uncertain significance not provided 2022-08-15 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt WFS1 protein function. ClinVar contains an entry for this variant (Variation ID: 1393805). This variant has not been reported in the literature in individuals affected with WFS1-related conditions. This variant is present in population databases (rs769151204, gnomAD 0.03%). This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 275 of the WFS1 protein (p.Ala275Gly).
Fulgent Genetics, Fulgent Genetics RCV002482733 SCV002793512 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2021-11-13 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV001884628 SCV004847270 uncertain significance not provided 2023-02-27 criteria provided, single submitter clinical testing The p.Ala275Gly variant in WFS1 has not been previously reported in individuals with WFS1-related conditions but has been identified in 0.019% (8/41426) of African American chromosomes by gnomAD v. 3 (http://gnomad.broadinstitute.org). This variant has also been reported in ClinVar (Variation ID 1393805). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: none.
Ambry Genetics RCV004681296 SCV005174963 uncertain significance Inborn genetic diseases 2024-06-04 criteria provided, single submitter clinical testing The c.824C>G (p.A275G) alteration is located in exon 7 (coding exon 6) of the WFS1 gene. This alteration results from a C to G substitution at nucleotide position 824, causing the alanine (A) at amino acid position 275 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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