ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.7762del (p.Ile2588fs)
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.7762del (p.Ile2588fs)
Variation ID: 52405 Accession: VCV000052405.10
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 13q13.1 13: 32357886 (GRCh38) [ NCBI UCSC ] 13: 32932023 (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 1, 2014 Jul 29, 2023 Sep 8, 2016 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000059.4:c.7762del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Ile2588fs frameshift NM_000059.3:c.7762delA NC_000013.11:g.32357886del NC_000013.10:g.32932023del NG_012772.3:g.47407del LRG_293:g.47407del U43746.1:n.7990delA - Protein change
- I2588fs
- Other names
- 7990del3ins2
- 7990delA
- Canonical SPDI
- NC_000013.11:32357885: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 |
- | 18602 |
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
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
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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) |
criteria provided, multiple submitters, no conflicts
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Jun 5, 2023 | RCV000045307.15 | |
Pathogenic (3) |
reviewed by expert panel
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Sep 8, 2016 | RCV000113814.13 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 18, 2018 | RCV000509870.11 |
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
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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
(Sep 08, 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: SCV000301202.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
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Pathogenic
(Jun 05, 2023)
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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: SCV004021071.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
Variant summary: BRCA2 c.7762delA (p.Ile2588TyrfsX60) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is … (more)
Variant summary: BRCA2 c.7762delA (p.Ile2588TyrfsX60) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant was absent in 251436 control chromosomes (gnomAD). c.7762delA has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (Lilyquist_2017). The following publication has been ascertained in the context of this evaluation (PMID: 28888541). Four submitters, including an expert panel, have provided clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Oct 01, 2016)
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criteria provided, single submitter
Method: research
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Hereditary breast and ovarian cancer
Affected status: no
Allele origin:
germline
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CSER _CC_NCGL, University of Washington
Study: CSER - NEXT Medicine variant annotation
Accession: SCV000700127.1 First in ClinVar: Mar 23, 2018 Last updated: Mar 23, 2018 |
Comment:
Found in a male patient having exome sequencing for an unrelated indication with a family history of breast and pancreatic cancer. This interpretation considers GERP … (more)
Found in a male patient having exome sequencing for an unrelated indication with a family history of breast and pancreatic cancer. This interpretation considers GERP score and allele frequency data, in addition to published reports of the variant in the literature, available at the time of review. (less)
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Pathogenic
(Apr 18, 2018)
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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: SCV000608142.4
First in ClinVar: Oct 23, 2017 Last updated: Nov 29, 2022 |
Comment:
The c.7762delA pathogenic mutation, located in coding exon 15 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 7762, causing … (more)
The c.7762delA pathogenic mutation, located in coding exon 15 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 7762, causing a translational frameshift with a predicted alternate stop codon (p.I2588Yfs*60). This pathogenic mutation has been reported in an early-onset breast cancer family and in a series of >900 epithelial ovarian cancer patients (Frank TS et al. J. Clin. Oncol. 1998 Jul;16:2417-25; Cunningham JM et al. Sci Rep. 2014 Feb;4:4026). In one case control study, this alteration was detected in 2/2222 individuals with high-grade serous epithelial ovarian cancer and 0/1528 matched controls. (Song H et al. Hum. Mol. Genet. 2014 Sep;23:4703-9). Of note, this mutation is also designated as 7990delA and I2588fs in published 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)
Number of individuals with the variant: 1
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Pathogenic
(May 11, 2022)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
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Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002556628.2
First in ClinVar: Aug 08, 2022 Last updated: Dec 17, 2022 |
Comment:
The BRCA2 c.7762del variant is classified as Pathogenic (PVS1, PS4_Moderate, PM2) This BRCA2 c.7762del variant is located in exon 16/27 and is predicted to cause … (more)
The BRCA2 c.7762del variant is classified as Pathogenic (PVS1, PS4_Moderate, PM2) This BRCA2 c.7762del variant is located in exon 16/27 and is predicted to cause a shift in the reading frame at codon 2588. BRCA2:c. 7762del (also described as BRCA1 4184del4 using legacy nomenclature) has been reported in multiple unrelated individuals and families with breast, ovarian and colon cancer (Cunningham et al., 2015 PMID: 24504028; Rosenthal et al, 2018 PMID: 30267214; Copson et al, 2018 PMID: 29337092). (Ps4_moderate) The variant has been reported in dbSNP (rs80359679) and has been reported as Pathogenic by other diagnostic laboratories (ClinVar Variation ID: 52405). It has not been reported in HGMD. literature: Frank (1998) J Clin Oncol, Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. PubMed: 9667259 (less)
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Pathogenic
(Jun 12, 2000)
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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
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Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000147176.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 1
Observation 2:
Number of individuals with the variant: 1
Geographic origin: Western European
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Pathogenic
(Jun 11, 2014)
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no assertion criteria provided
Method: clinical testing
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BRCA1 and BRCA2 Hereditary Breast and Ovarian Cancer
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000073320.3
First in ClinVar: Jul 03, 2013 Last updated: Jun 15, 2014 |
Comment:
The interpretation for this sequence variant was made by Invitae based on the ACMG guidelines. A more detailed explanation of the interpretation for this specific … (more)
The interpretation for this sequence variant was made by Invitae based on the ACMG guidelines. A more detailed explanation of the interpretation for this specific variant is forthcoming. This ClinVar entry will be updated at that time. (less)
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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: SCV000587907.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
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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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Rare loss of function variants in candidate genes and risk of colorectal cancer. | Rosenthal EA | Human genetics | 2018 | PMID: 30267214 |
Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study. | Copson ER | The Lancet. Oncology | 2018 | PMID: 29337092 |
Frequency of mutations in a large series of clinically ascertained ovarian cancer cases tested on multi-gene panels compared to reference controls. | Lilyquist J | Gynecologic oncology | 2017 | PMID: 28888541 |
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 |
Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status. | Cunningham JM | Scientific reports | 2014 | PMID: 24504028 |
Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. | Frank TS | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 1998 | PMID: 9667259 |
Text-mined citations for rs80359679 ...
HelpRecord last updated Apr 15, 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.