Leu734Leu in Exon 08 of WFS1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.1% (2/3728) of Afric an American chromosomes from a broad population by the NHLBI Exome Sequencing Pr oject (http://evs.gs.washington.edu/EVS; dbSNP rs140427062).
ClinVar Genomic variation as it relates to human health
NM_006005.3(WFS1):c.2202C>T (p.Leu734=)
Germline
Classification
Help
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.
(9)
Help
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.
Benign/Likely benign
9
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_006005.3(WFS1):c.2202C>T (p.Leu734=)
Variation ID: 45450 Accession: VCV000045450.23
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 4p16.1 4: 6301997 (GRCh38) [ NCBI UCSC ] 4: 6303724 (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 Apr 9, 2018 Sep 29, 2024 Jan 29, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_006005.3:c.2202C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005996.2:p.Leu734= synonymous NM_001145853.1:c.2202C>T NP_001139325.1:p.Leu734= synonymous NC_000004.12:g.6301997C>T NC_000004.11:g.6303724C>T NG_011700.1:g.37148C>T LRG_1417:g.37148C>T LRG_1417t1:c.2202C>T LRG_1417p1:p.Leu734= - Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000004.12:6301996:C:T
-
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.
-
0.00040 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
The Genome Aggregation Database (gnomAD), exomes 0.00019
Exome Aggregation Consortium (ExAC) 0.00021
1000 Genomes Project 0.00040
The Genome Aggregation Database (gnomAD) 0.00041
Trans-Omics for Precision Medicine (TOPMed) 0.00046
1000 Genomes Project 30x 0.00047
- Links
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 |
1753 | 1854 | |
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 (3) |
criteria provided, multiple submitters, no conflicts
|
Jul 29, 2021 | RCV000038654.13 | |
| Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
|
Jan 29, 2024 | RCV000876954.12 | |
| Benign (1) |
criteria provided, single submitter
|
- | RCV003125864.1 |
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
(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: SCV000062332.6
First in ClinVar: May 03, 2013 Last updated: Apr 09, 2018 |
Comment:
Leu734Leu in Exon 08 of WFS1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, … (more)
Leu734Leu in Exon 08 of WFS1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.1% (2/3728) of Afric an American chromosomes from a broad population by the NHLBI Exome Sequencing Pr oject (http://evs.gs.washington.edu/EVS; dbSNP rs140427062). (less)
Number of individuals with the variant: 1
|
|
|
Likely benign
(Jul 29, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002066700.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
|
|
|
Benign
(-)
|
criteria provided, single submitter
(K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)
Method: research
|
Wolfram syndrome 1
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
|
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic
Accession: SCV003802936.1
First in ClinVar: Feb 18, 2023 Last updated: Feb 18, 2023 |
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 … (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 rs140427062 in Wolfram's syndrome yet. (less)
|
|
|
Likely benign
(May 05, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000722919.3
First in ClinVar: Apr 09, 2018 Last updated: Mar 04, 2023 |
|
|
|
Benign
(Jan 29, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001019602.4
First in ClinVar: Dec 17, 2019 Last updated: Feb 28, 2024 |
|
|
|
Likely benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005257175.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
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: SCV001966518.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
|
|
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: SCV002037022.1 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: SCV001922413.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
Comment:
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 sufficient evidence is found to ascertain the role of this particular variant rs140427062 in Wolfram's syndrome yet.
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. |
Comment:
Leu734Leu in Exon 08 of WFS1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.1% (2/3728) of Afric an American chromosomes from a broad population by the NHLBI Exome Sequencing Pr oject (http://evs.gs.washington.edu/EVS; dbSNP rs140427062).
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 sufficient evidence is found to ascertain the role of this particular variant rs140427062 in Wolfram's syndrome yet.
Citations for germline classification of this variant
Help| Title | 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 |
| 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 |
Text-mined citations for rs140427062 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 29, 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.