ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.7934del (p.Arg2645fs)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000059.4(BRCA2):c.7934del (p.Arg2645fs)
Variation ID: 52440 Accession: VCV000052440.48
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 13q13.1 13: 32362651 (GRCh38) [ NCBI UCSC ] 13: 32936788 (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 Sep 27, 2014 Jun 17, 2024 Apr 22, 2016 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000059.4:c.7934del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Arg2645fs frameshift NM_000059.3:c.7934delG NC_000013.11:g.32362651del NC_000013.10:g.32936788del NG_012772.3:g.52172del LRG_293:g.52172del U43746.1:n.8162delG - Protein change
- R2645fs
- Other names
- NP_000050.3:p.Arg2645AsnfsTer3
- 8162delG
- Canonical SPDI
- NC_000013.11:32362650:G:
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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 |
18773 | 18931 |
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 (4) |
reviewed by expert panel
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Apr 22, 2016 | RCV000077418.17 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Dec 29, 2023 | RCV000132051.18 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jan 28, 2024 | RCV000257923.23 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Feb 22, 2022 | RCV000506376.13 | |
not provided (1) |
no classification provided
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- | RCV001535707.10 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 6, 2021 | RCV003149692.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 8, 2022 | RCV003473410.1 |
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
(Apr 22, 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: SCV000282452.1
First in ClinVar: Jun 24, 2016 Last updated: Jun 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
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Pathogenic
(Jul 12, 2016)
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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: SCV000695109.1
First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017 |
Comment:
Variant summary: The BRCA2 c.7934delG (p.Arg2645Asnfs) variant located in the helical domain (Interpro) results in a premature termination codon, predicted to cause a truncated or … (more)
Variant summary: The BRCA2 c.7934delG (p.Arg2645Asnfs) variant located in the helical domain (Interpro) results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant of interest was not observed in controls (ExAC, 1000 Gs or ESP) and has been reported in multiple affected individuals. The variant of interest has been indicated to be an Afrikaner founder mutation. Multiple reputable databases/clinical laboratories cite the variant as "pathogenic." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Pathogenic. (less)
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Pathogenic
(Apr 19, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
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National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Accession: SCV002025834.2
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 21
Geographic origin: South Africa
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Pathogenic
(Oct 06, 2021)
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criteria provided, single submitter
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV003838835.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
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Pathogenic
(Sep 08, 2022)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004210496.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Feb 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003812408.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Dec 29, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV001356102.3
First in ClinVar: Jun 22, 2020 Last updated: Feb 14, 2024 |
Comment:
This variant deletes 1 nucleotide in exon 17 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant deletes 1 nucleotide in exon 17 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant is a well-known South African founder mutation and has been reported in more than 10 individuals affected with breast and ovarian cancer (PMID: 8988179, 22638694, 23885733, 24728189, 26577449, 26915939, 32375709, 33471991; Leiden Open Variation Database DB-ID BRCA2_001450, 34660253, Color internal data). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(Jan 28, 2024)
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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: SCV000073361.12
First in ClinVar: Jul 03, 2013 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg2645Asnfs*3) in the BRCA2 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg2645Asnfs*3) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 8988179, 22638694, 23885733, 24728189, 26577449, 26915939). This variant is also known as 8162delG. ClinVar contains an entry for this variant (Variation ID: 52440). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jul 12, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000187113.9
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The c.7934delG pathogenic mutation, located in coding exon 16 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 7934, causing … (more)
The c.7934delG pathogenic mutation, located in coding exon 16 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 7934, causing a translational frameshift with a predicted alternate stop codon (p.R2645Nfs*3). This pathogenic mutation has been reported in one family with three individuals affected with breast cancer at or under the age of 60 (Gayther SA et al. Nat Genet. 1997 Jan;15(1):103-5). This pathogenic mutation is also a well described African founder mutation (van der Merwe NC et al. Clin Genet. 2012 Feb;81(2):179-84; Schoeman M et al. S Afr Med J. 2013 Jun 25;103(8):529-33; Meyer S et al. J Med Genet. 2014 Feb;51(2):71-5; Seymour HJ et al. S. Afr. Med. J., 2016 Feb;106:264-7). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Of note, this may also be referred to as 8162delG in some literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Jun 12, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000600772.2
First in ClinVar: Sep 30, 2017 Last updated: Jan 03, 2022 |
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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: SCV000327767.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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Pathogenic
(Mar 30, 2012)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 2
Affected status: not provided
Allele origin:
germline
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Sharing Clinical Reports Project (SCRP)
Accession: SCV000109216.2
First in ClinVar: Dec 23, 2013 Last updated: Sep 27, 2014 |
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Pathogenic
(Mar 23, 1999)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 2
Affected status: yes
Allele origin:
germline,
unknown
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Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000147222.2
First in ClinVar: Apr 01, 2014 Last updated: Mar 29, 2015 |
Observation 1:
Number of individuals with the variant: 1
Ethnicity/Population group: Mixed Ancestry, Caucasian
Geographic origin: South Africa
Observation 2:
Number of individuals with the variant: 1
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Pathogenic
(Jan 31, 2014)
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no assertion criteria provided
Method: research
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Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
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Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587922.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
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not provided
(-)
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no classification provided
Method: phenotyping only
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Hereditary breast ovarian cancer syndrome
Fanconi anemia complementation group D1
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
unknown
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GenomeConnect - Invitae Patient Insights Network
Accession: SCV001749791.2
First in ClinVar: Jul 18, 2021 Last updated: Jun 17, 2024 |
Comment:
Variant interpreted as Pathogenic and reported on 10-07-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report … (more)
Variant interpreted as Pathogenic and reported on 10-07-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less)
Clinical Features:
Abnormality of vision (present) , Myopia (present) , Obesity (present) , Hyperthyroidism (present) , Abnormal delivery (present)
Indication for testing: Diagnostic
Age: 50-59 years
Sex: female
Testing laboratory: Invitae
Date variant was reported to submitter: 2020-10-07
Testing laboratory interpretation: Pathogenic
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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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Prevalence of Clinically Relevant Germline BRCA Variants in a Large Unselected South African Breast and Ovarian Cancer Cohort: A Public Sector Experience. | Van der Merwe NC | Frontiers in genetics | 2022 | DOI: 10.3389/fgene.2022.834265 |
Pioneering BRCA1/2 Point-Of-Care Testing for Integration of Germline and Tumor Genetics in Breast Cancer Risk Management: A Vision for the Future of Translational Pharmacogenomics. | Mampunye L | Frontiers in oncology | 2021 | PMID: 34660253 |
Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
The contribution of large genomic rearrangements in BRCA1 and BRCA2 to South African familial breast cancer. | van der Merwe NC | BMC cancer | 2020 | PMID: 32375709 |
Breast cancer in high-risk Afrikaner families: Is BRCA founder mutation testing sufficient? | Seymour HJ | South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde | 2016 | PMID: 26915939 |
BRCA1, BRCA2 and PALB2 mutations and CHEK2 c.1100delC in different South African ethnic groups diagnosed with premenopausal and/or triple negative breast cancer. | Francies FZ | BMC cancer | 2015 | PMID: 26577449 |
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 | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
The contribution of deleterious germline mutations in BRCA1, BRCA2 and the mismatch repair genes to ovarian cancer in the population. | Song H | Human molecular genetics | 2014 | PMID: 24728189 |
Implementation of a breast cancer genetic service in South Africa - lessons learned. | Schoeman M | South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde | 2013 | PMID: 23885733 |
CYP2D6 genotyping and use of antidepressants in breast cancer patients: test development for clinical application. | van der Merwe N | Metabolic brain disease | 2012 | PMID: 22638694 |
A founder BRCA2 mutation in non-Afrikaner breast cancer patients of the Western Cape of South Africa. | van der Merwe NC | Clinical genetics | 2012 | PMID: 21204799 |
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 |
Variation of risks of breast and ovarian cancer associated with different germline mutations of the BRCA2 gene. | Gayther SA | Nature genetics | 1997 | PMID: 8988179 |
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Text-mined citations for rs80359688 ...
HelpRecord last updated Jul 07, 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.