ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.93G>A (p.Trp31Ter)
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_000059.4(BRCA2):c.93G>A (p.Trp31Ter)
Variation ID: 52829 Accession: VCV000052829.12
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q13.1 13: 32319102 (GRCh38) [ NCBI UCSC ] 13: 32893239 (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 Oct 22, 2016 Feb 28, 2024 Oct 18, 2016 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000059.4:c.93G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Trp31Ter nonsense NC_000013.11:g.32319102G>A NC_000013.10:g.32893239G>A NG_012772.3:g.8623G>A NG_017006.2:g.1262C>T LRG_293:g.8623G>A LRG_293t1:c.93G>A LRG_293p1:p.Trp31Ter - Protein change
- W31*
- Other names
- 0321G>A (W31X)
- Canonical SPDI
- NC_000013.11:32319101:G:A
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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BRCA2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
18441 | 18600 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Sep 8, 2022 | RCV000045810.19 | |
Pathogenic (2) |
reviewed by expert panel
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Oct 18, 2016 | RCV000256653.13 |
Submissions - Germline
Classification
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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
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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
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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
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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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Pathogenic
(Oct 18, 2016)
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reviewed by expert panel
Method: curation
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
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Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000324771.2
First in ClinVar: Oct 22, 2016 Last updated: Feb 07, 2023 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
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Pathogenic
(Jul 29, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002571079.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
Variant summary: BRCA2 c.93G>A (p.Trp31X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: BRCA2 c.93G>A (p.Trp31X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250830 control chromosomes (gnomAD). c.93G>A has been reported in the literature in individuals affected with Hereditary Breast And/or Ovarian Cancer Syndrome (examples: Rebbeck_2018 and Zheng_2018). At least one publication reports experimental evidence demonstating an impact on protein function (Mesman_BRCA2_GIM_2020). These data indicate that the variant is likely to be associated with disease. Four submitters including an expert panel (ENIGMA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Oct 02, 2015)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
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Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000328124.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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Pathogenic
(Jul 02, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV000838720.2
First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022 |
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Pathogenic
(Sep 08, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000073823.9
First in ClinVar: Jul 03, 2013 Last updated: Feb 28, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 52829). This variant is also known … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 52829). This variant is also known as 321G>A. This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 17080309, 22009639, 22776961, 26911350). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp31*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). (less)
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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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Alternative mRNA splicing can attenuate the pathogenicity of presumed loss-of-function variants in BRCA2. | Mesman RLS | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 32398771 |
Inherited Breast Cancer in Nigerian Women. | Zheng Y | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2018 | PMID: 30130155 |
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
Detection of high frequency of mutations in a breast and/or ovarian cancer cohort: implications of embracing a multi-gene panel in molecular diagnosis in India. | Mannan AU | Journal of human genetics | 2016 | PMID: 26911350 |
Germline BRCA1 and BRCA2 mutations in ovarian cancer: utility of a histology-based referral strategy. | Schrader KA | Obstetrics and gynecology | 2012 | PMID: 22776961 |
Predictive factors for BRCA1/BRCA2 mutations in women with ductal carcinoma in situ. | Bayraktar S | Cancer | 2012 | PMID: 22009639 |
Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
High proportion of BRCA1/2 founder mutations in Hispanic breast/ovarian cancer families from Colombia. | Torres D | Breast cancer research and treatment | 2007 | PMID: 17080309 |
Text-mined citations for rs80359214 ...
HelpRecord last updated Mar 23, 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.