NM_006005.3(WFS1):c.1957C>T (p.Arg653Cys) AND Autosomal dominant nonsyndromic deafness 6

Clinical significance:Uncertain significance (Last evaluated: May 31, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000677339.2

Allele description [Variation Report for NM_006005.3(WFS1):c.1957C>T (p.Arg653Cys)]

NM_006005.3(WFS1):c.1957C>T (p.Arg653Cys)

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.1957C>T (p.Arg653Cys)
Other names:
p.R653C:CGC>TGC; NM_001145853.1(WFS1):c.1957C>T(p.Arg653Cys); NM_006005.3(WFS1):c.1957C>T(p.Arg653Cys)
HGVS:
  • NC_000004.12:g.6301752C>T
  • NG_011700.1:g.36903C>T
  • NM_001145853.1:c.1957C>T
  • NM_006005.3:c.1957C>TMANE SELECT
  • NP_001139325.1:p.Arg653Cys
  • NP_005996.2:p.Arg653Cys
  • LRG_1417t1:c.1957C>T
  • LRG_1417:g.36903C>T
  • LRG_1417p1:p.Arg653Cys
  • NC_000004.11:g.6303479C>T
  • O76024:p.Arg653Cys
Protein change:
R653C
Links:
UniProtKB: O76024#VAR_014037; dbSNP: rs201064551
NCBI 1000 Genomes Browser:
rs201064551
Molecular consequence:
  • NM_001145853.1:c.1957C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006005.3:c.1957C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Autosomal dominant nonsyndromic deafness 6 (DFNA6)
Synonyms:
DEAFNESS, AUTOSOMAL DOMINANT 6; DEAFNESS, AUTOSOMAL DOMINANT 14; DEAFNESS, AUTOSOMAL DOMINANT 38; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010963; MedGen: C1833021; Orphanet: 90635; OMIM: 600965

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000803617SIB Swiss Institute of Bioinformaticscriteria provided, single submitter
Uncertain significance
(May 31, 2018)
unknowncuration

PubMed (2)
[See all records that cite these PMIDs]

SCV001313297Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Apr 27, 2017)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Targeted genomic capture and massively parallel sequencing to identify novel variants causing Chinese hereditary hearing loss.

Wei Q, Zhu H, Qian X, Chen Z, Yao J, Lu Y, Cao X, Xing G.

J Transl Med. 2014 Nov 12;12:311. doi: 10.1186/s12967-014-0311-1.

PubMed [citation]
PMID:
25388789
PMCID:
PMC4234825

Details of each submission

From SIB Swiss Institute of Bioinformatics, SCV000803617.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (2)

Description

This variant is interpreted as a Uncertain Significance - Conflicting Evidence, for Deafness, in Autosomal Dominant manner. The following ACMG Tag(s) were applied: PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:25388789). BS1 => Allele frequency is greater than expected for disorder.

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

From Illumina Clinical Services Laboratory,Illumina, SCV001313297.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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

Last Updated: Jul 7, 2021

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