ClinVar Genomic variation as it relates to human health
NM_006005.3(WFS1):c.2335G>A (p.Val779Met)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain risk allele(1); Benign(6); Likely benign(4)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_006005.3(WFS1):c.2335G>A (p.Val779Met)
Variation ID: 45453 Accession: VCV000045453.34
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 4p16.1 4: 6302130 (GRCh38) [ NCBI UCSC ] 4: 6303857 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 6, 2016 Feb 20, 2024 Jan 25, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_006005.3:c.2335G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005996.2:p.Val779Met missense NM_001145853.1:c.2335G>A NP_001139325.1:p.Val779Met missense NC_000004.12:g.6302130G>A NC_000004.11:g.6303857G>A NG_011700.1:g.37281G>A LRG_1417:g.37281G>A LRG_1417t1:c.2335G>A LRG_1417p1:p.Val779Met O76024:p.Val779Met - Protein change
- V779M
- Other names
- -
- Canonical SPDI
- NC_000004.12:6302129:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.00659 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00659
The Genome Aggregation Database (gnomAD) 0.00672
Trans-Omics for Precision Medicine (TOPMed) 0.00695
1000 Genomes Project 30x 0.00734
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00824
Exome Aggregation Consortium (ExAC) 0.00221
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
WFS1 | No evidence available | No evidence available |
GRCh38 GRCh37 |
1725 | 1825 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Likely benign (1) |
criteria provided, single submitter
|
Apr 28, 2017 | RCV000404342.7 | |
Likely benign (1) |
criteria provided, single submitter
|
Apr 28, 2017 | RCV000300529.7 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Jan 25, 2024 | RCV000515097.20 | |
Benign (1) |
criteria provided, single submitter
|
Sep 7, 2018 | RCV000664095.5 | |
Uncertain risk allele (1) |
criteria provided, single submitter
|
- | RCV002464005.3 | |
Likely benign (1) |
criteria provided, single submitter
|
Apr 25, 2022 | RCV002496613.3 | |
Benign (5) |
criteria provided, multiple submitters, no conflicts
|
May 26, 2016 | RCV000038657.15 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Likely benign
(May 15, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000610765.1
First in ClinVar: Nov 05, 2017 Last updated: Nov 05, 2017 |
|
|
Benign
(Jun 23, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000252500.11
First in ClinVar: Oct 11, 2015 Last updated: Dec 06, 2016 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
|
Benign
(May 26, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000341012.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 1
Sex: mixed
|
|
Benign
(Apr 30, 2012)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000062335.6
First in ClinVar: May 03, 2013 Last updated: Dec 06, 2016 |
Comment:
Val779Met in Exon 08 of WFS1: This variant is not expected to have clinical sign ificance because it has been identified in 2.5% (92/3730) of … (more)
Val779Met in Exon 08 of WFS1: This variant is not expected to have clinical sign ificance because it has been identified in 2.5% (92/3730) of African American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS; dbSNP rs141328044). (less)
Number of individuals with the variant: 16
|
|
Likely benign
(Apr 28, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
WFS1-Related Spectrum Disorders
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000450671.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
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, … (more)
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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
Likely benign
(Apr 28, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal dominant nonsyndromic hearing loss 6
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000450672.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
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, … (more)
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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
Uncertain risk allele
(-)
|
criteria provided, single submitter
(K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)
Method: research
|
Wolfram syndrome 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
unknown
|
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic
Accession: SCV002605296.1
First in ClinVar: Dec 11, 2022 Last updated: Dec 11, 2022 |
Comment:
Potent mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy.However no … (more)
Potent mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy.However no sufficient evidence is found to ascertain the role of this particular variant rs141328044 yet. (less)
|
|
Benign
(Sep 07, 2018)
|
criteria provided, single submitter
Method: research
|
Monogenic diabetes
Affected status: unknown
Allele origin:
unknown
|
Personalized Diabetes Medicine Program, University of Maryland School of Medicine
Accession: SCV000787547.2
First in ClinVar: Jul 21, 2018 Last updated: Jun 13, 2020 |
Comment:
ACMG criteria: BA1 (2.2% in gnomAD Africans), BS2 (72 cases and 71 controls in T2DM genes) (REVEL 0.696 + PP3/7 predictors + BP4/2 predictors= conflicting … (more)
ACMG criteria: BA1 (2.2% in gnomAD Africans), BS2 (72 cases and 71 controls in T2DM genes) (REVEL 0.696 + PP3/7 predictors + BP4/2 predictors= conflicting evidence, not using); Note: papers associate variant with LFHL (PMID: 11709537, 12955714)=benign (less)
Number of individuals with the variant: 4
|
|
Likely benign
(Apr 25, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Cataract 41
Type 2 diabetes mellitus Wolfram syndrome 1 Autosomal dominant nonsyndromic hearing loss 6 Wolfram-like syndrome
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002810087.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
Benign
(Jan 25, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001012011.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
|
|
Benign
(Nov 22, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002506004.3
First in ClinVar: May 07, 2022 Last updated: Feb 20, 2024 |
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002036152.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001921627.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001969270.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
|
click to load more click to collapse |
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
WFS1 Spectrum Disorder. | Adam MP | - | 2022 | PMID: 20301750 |
A novel mutation of WFS1 gene leading to increase ER stress and cell apoptosis is associated an autosomal dominant form of Wolfram syndrome type 1. | Gong Y | BMC endocrine disorders | 2021 | PMID: 33879153 |
Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants. | Shearer AE | American journal of human genetics | 2014 | PMID: 25262649 |
Exome sequencing in the clinical diagnosis of sporadic or familial cerebellar ataxia. | Fogel BL | JAMA neurology | 2014 | PMID: 25133958 |
Wolfram syndrome and WFS1 gene. | Rigoli L | Clinical genetics | 2011 | PMID: 20738327 |
Testing of diabetes-associated WFS1 polymorphisms in the Diabetes Prevention Program. | Florez JC | Diabetologia | 2008 | PMID: 18060660 |
Common variants in WFS1 confer risk of type 2 diabetes. | Sandhu MS | Nature genetics | 2007 | PMID: 17603484 |
Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease. | Cryns K | Human mutation | 2003 | PMID: 12955714 |
Mutations in the Wolfram syndrome 1 gene (WFS1) are a common cause of low frequency sensorineural hearing loss. | Bespalova IN | Human molecular genetics | 2001 | PMID: 11709537 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=WFS1 | - | - | - | - |
type2diabetesgenetics.org | - | - | - | - |
click to load more click to collapse |
Text-mined citations for rs141328044 ...
HelpRecord last updated May 12, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.