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NM_006005.3(WFS1):c.1672C>T (p.Arg558Cys) AND WFS1-related disorder

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Nov 25, 2023
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV004537507.2

Allele description [Variation Report for NM_006005.3(WFS1):c.1672C>T (p.Arg558Cys)]

NM_006005.3(WFS1):c.1672C>T (p.Arg558Cys)

Gene:
WFS1:wolframin ER transmembrane glycoprotein [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4p16.1
Genomic location:
Preferred name:
NM_006005.3(WFS1):c.1672C>T (p.Arg558Cys)
HGVS:
  • NC_000004.12:g.6301467C>T
  • NG_011700.1:g.36618C>T
  • NM_001145853.1:c.1672C>T
  • NM_006005.3:c.1672C>TMANE SELECT
  • NP_001139325.1:p.Arg558Cys
  • NP_005996.2:p.Arg558Cys
  • LRG_1417t1:c.1672C>T
  • LRG_1417:g.36618C>T
  • LRG_1417p1:p.Arg558Cys
  • NC_000004.11:g.6303194C>T
  • O76024:p.Arg558Cys
Protein change:
R558C
Links:
UniProtKB: O76024#VAR_068343; dbSNP: rs199946797
NCBI 1000 Genomes Browser:
rs199946797
Molecular consequence:
  • NM_001145853.1:c.1672C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006005.3:c.1672C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
WFS1-related disorder
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004114884PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Likely pathogenic
(Nov 25, 2023) 		germlineclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004114884.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The WFS1 c.1672C>T variant is predicted to result in the amino acid substitution p.Arg558Cys. This variant was reported in the compound heterozygous and homozygous states in individuals with features of Wolfram syndrome (Cano et al. 2007. PubMed ID: 17568405; Lieber et al 2012. PubMed ID: 22226368; Ustaoglu et al 2019. PubMed ID: 30957632). This variant has also been reported, with uncertain significance, in an individual with sporadic ataxia (Fogel et al 2014. PubMed ID: 25133958) and in an individual with schizophrenia (Torres et al 2001. PubMed ID: 11244483). This variant is reported in 1.3% of alleles in individuals of Ashkenazi Jewish descent in gnomAD, including one homozygote. This variant in the homozygous state was found to significantly increase risk for type 1 diabetes in a cohort of Ashkenazi Jewish patients, although age at diabetes diagnosis was later than usual and other features of Wolfram syndrome were absent in most patients, suggesting this variant has a mild effect compared to other Wolfram syndrome causative variants (Bansal et al. 2018. PubMed ID: 30014265). This variant is interpreted as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 26, 2024