ClinVar Genomic variation as it relates to human health
NM_000553.6(WRN):c.2500C>T (p.Arg834Cys)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000553.6(WRN):c.2500C>T (p.Arg834Cys)
Variation ID: 38888 Accession: VCV000038888.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 8p12 8: 31120294 (GRCh38) [ NCBI UCSC ] 8: 30977810 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 4, 2013 Feb 28, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000553.6:c.2500C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000544.2:p.Arg834Cys missense NC_000008.11:g.31120294C>T NC_000008.10:g.30977810C>T NG_008870.1:g.92033C>T LRG_524:g.92033C>T LRG_524t1:c.2500C>T Q14191:p.Arg834Cys - Protein change
- R834C
- Other names
- -
- Canonical SPDI
- NC_000008.11:31120293:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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0.00180 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00089
Trans-Omics for Precision Medicine (TOPMed) 0.00171
1000 Genomes Project 0.00180
1000 Genomes Project 30x 0.00187
Exome Aggregation Consortium (ExAC) 0.00208
The Genome Aggregation Database (gnomAD), exomes 0.00283
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 | ||
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HI score
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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. |
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WRN | - | - |
GRCh38 GRCh37 |
3620 | 3777 |
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. |
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Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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Jan 31, 2024 | RCV000032137.17 | |
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Mar 18, 2022 | RCV000122280.6 |
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. |
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Benign
(Jan 28, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000227777.5
First in ClinVar: Jun 28, 2015 Last updated: Jun 28, 2015 |
Number of individuals with the variant: 2
Sex: mixed
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Likely benign
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Werner syndrome
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001325359.1
First in ClinVar: May 31, 2020 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)
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Benign
(Dec 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Werner syndrome
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002514982.1
First in ClinVar: May 21, 2022 Last updated: May 21, 2022 |
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Likely benign
(Mar 18, 2022)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002500466.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Werner syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000285538.9
First in ClinVar: Apr 04, 2013 Last updated: Feb 28, 2024 |
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not provided
(-)
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no classification provided
Method: literature only
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Werner syndrome
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV000055695.2
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
Comment:
Variant common in Latino population (heterozygote frequency of 0.02); significantly reduces helicase & exonuclease activity in vitro. Homozygotes do not exhibit a Werner syndrome phenotype
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not provided
(Sep 19, 2013)
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no classification provided
Method: reference population
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AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
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ITMI
Accession: SCV000086505.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
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Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
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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 |
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Werner Syndrome. | Adam MP | - | 2021 | PMID: 20301687 |
Homozygosity for the WRN Helicase-Inactivating Variant, R834C, does not confer a Werner syndrome clinical phenotype. | Kamath-Loeb AS | Scientific reports | 2017 | PMID: 28276523 |
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing. | Bodian DL | PloS one | 2014 | PMID: 24728327 |
Aging is accompanied by a progressive decrease of expression of the WRN gene in human blood mononuclear cells. | Polosak J | The journals of gerontology. Series A, Biological sciences and medical sciences | 2011 | PMID: 20855428 |
WRN helicase defective in the premature aging disorder Werner syndrome genetically interacts with topoisomerase 3 and restores the top3 slow growth phenotype of sgs1 top3. | Aggarwal M | Aging | 2009 | PMID: 20157511 |
The enzymatic activities of the Werner syndrome protein are disabled by the amino acid polymorphism R834C. | Kamath-Loeb AS | The Journal of biological chemistry | 2004 | PMID: 15489508 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=WRN | - | - | - | - |
http://www.pathology.washington.edu/research/werner/database/ | - | - | - | - |
Text-mined citations for rs3087425 ...
HelpRecord last updated Mar 05, 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.