ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.778_779del (p.Glu260fs)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000059.4(BRCA2):c.778_779del (p.Glu260fs)
Variation ID: 38119 Accession: VCV000038119.31
- Type and length
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Microsatellite, 2 bp
- Location
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Cytogenetic: 13q13.1 13: 32331012-32331013 (GRCh38) [ NCBI UCSC ] 13: 32905149-32905150 (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 Sep 16, 2024 Apr 22, 2016 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000059.4:c.778_779del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Glu260fs frameshift NM_000059.3:c.778_779delGA NC_000013.11:g.32331013GA[1] NC_000013.10:g.32905150GA[1] NG_012772.3:g.20534GA[1] LRG_293:g.20534GA[1] U43746.1:n.1006_1007delGA - Protein change
- E260fs
- Other names
- 1003delAG
- 1006delGA
- Canonical SPDI
- NC_000013.11:32331011:AGAGA:AGA
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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 |
18955 | 19114 |
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 (5) |
reviewed by expert panel
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Apr 22, 2016 | RCV000031701.20 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 9, 2023 | RCV000045311.20 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jun 17, 2021 | RCV000131854.19 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Dec 17, 2023 | RCV000203632.22 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 10, 2023 | RCV003460530.2 |
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: SCV000282450.1
First in ClinVar: Jan 02, 2016 Last updated: Jan 02, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
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Pathogenic
(Dec 17, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000073324.14
First in ClinVar: Jul 03, 2013 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Glu260Serfs*15) 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.Glu260Serfs*15) 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 or endometrial cancer (PMID: 8673090, 26681312, 28008555). This variant is also known as delAG at nucleotide 775. ClinVar contains an entry for this variant (Variation ID: 38119). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Nov 10, 2023)
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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: SCV004216002.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Jun 12, 2020)
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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: SCV000903407.3
First in ClinVar: May 19, 2019 Last updated: Jun 19, 2021 |
Comment:
This variant deletes 2 nucleotides in exon 9 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant deletes 2 nucleotides in exon 9 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. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with male and female breast cancer, endometrial cancer and pancreatic cancer (PMID: 8673090, 26681312, 28008555, 30274973). 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
(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: SCV000327728.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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Pathogenic
(Nov 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004846824.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Comment:
The c.778_779del (p.Glu260Serfs*15) variant in the BRCA2 gene is located on the exon 9 and is predicted to cause shift of reading frame that introduces … (more)
The c.778_779del (p.Glu260Serfs*15) variant in the BRCA2 gene is located on the exon 9 and is predicted to cause shift of reading frame that introduces a premature translation termination codon (p.Glu260Serfs*15), resulting in an absent or disrupted protein product. The variant has been reported in multiple individuals with breast cancer (PMID: 29446198, 32614418, 8673090). Loss-of-function variants of BRCA2 are known to be pathogenic (PMID: 8988179, 11897832, 29446198). The variant is reported in ClinVar as pathogenic (ID: 38119) and reviewed by the expert panel. The variant is absent in the general population database (gnomAD). Therefore, the c.778_779del (p.Glu260Serfs*15) variant of BRCA2 has been classified as pathogenic. (less)
Number of individuals with the variant: 1
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Pathogenic
(Oct 09, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000210708.16
First in ClinVar: Feb 24, 2015 Last updated: Sep 16, 2024 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (PMID: 28008555, 8673090, 30274973); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 775delAG and 1006delGA; This variant is associated with the following publications: (PMID: 26187060, 26681312, 28008555, 28152038, 28678401, 30274973, 8673090, 33619265, 33084842, 30787465, 20104584, 33471991, 29446198) (less)
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Pathogenic
(Aug 17, 2020)
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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:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695101.2
First in ClinVar: Dec 26, 2017 Last updated: Sep 14, 2020 |
Comment:
Variant summary: BRCA2 c.778_779delGA (p.Glu260SerfsX15) 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.778_779delGA (p.Glu260SerfsX15) 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 250522 control chromosomes. c.778_779delGA has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (example, Phelan_1996, Pritzlaff_2017, Susswein_2016, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. Six clinical diagnostic laboratories and one expert panel (ENIGMA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Aug 23, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296623.5
First in ClinVar: Jan 02, 2016 Last updated: Jan 06, 2024 |
Comment:
This frameshift variant causes the premature termination of BRCA2 protein synthesis. In addition, it has been reported in affected individuals with breast, endometrial, head and … (more)
This frameshift variant causes the premature termination of BRCA2 protein synthesis. In addition, it has been reported in affected individuals with breast, endometrial, head and pancreatic cancers (PMIDs: 26681312 (2015), 28008555 (2017), 28678401 (2017), and 30274973 (2018)). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Jun 17, 2021)
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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: SCV000186909.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The c.778_779delGA pathogenic mutation, located in coding exon 8 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 778 to … (more)
The c.778_779delGA pathogenic mutation, located in coding exon 8 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 778 to 779, causing a translational frameshift with a predicted alternate stop codon (p.E260Sfs*15). This alteration has been reported in individuals diagnosed with head and neck squamous cell carcinoma, endometrial, breast and pancreatic cancer (Susswein LR et al. Genet. Med., 2016 08;18:823-32; Chandrasekharappa SC et al. Cancer, 2017 Oct;123:3943-3954; Pritzlaff M et al. Breast Cancer Res Treat, 2017 02;161:575-586; Bannon SA et al. Cancer Prev Res (Phila), 2018 11;11:679-686; Dorling et al. N Engl J Med. 2021 02;384:428-439). Additionally, this alteration was identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620). 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
(Dec 06, 2010)
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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: SCV000054308.4
First in ClinVar: Apr 04, 2013 Last updated: Sep 27, 2014 |
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Pathogenic
(Feb 20, 2004)
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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: SCV000145720.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 3
Observation 2:
Number of individuals with the variant: 1
Geographic origin: Western European
Observation 3:
Number of individuals with the variant: 1
Ethnicity/Population group: Central/Eastern European
Observation 4:
Number of individuals with the variant: 5
Ethnicity/Population group: Western European
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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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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 |
Characterization of the Cancer Spectrum in Men With Germline BRCA1 and BRCA2 Pathogenic Variants: Results From the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). | Silvestri V | JAMA oncology | 2020 | PMID: 32614418 |
High Prevalence of Hereditary Cancer Syndromes and Outcomes in Adults with Early-Onset Pancreatic Cancer. | Bannon SA | Cancer prevention research (Philadelphia, Pa.) | 2018 | PMID: 30274973 |
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
Assessing the spectrum of germline variation in Fanconi anemia genes among patients with head and neck carcinoma before age 50. | Chandrasekharappa SC | Cancer | 2017 | PMID: 28678401 |
Male breast cancer in a multi-gene panel testing cohort: insights and unexpected results. | Pritzlaff M | Breast cancer research and treatment | 2017 | PMID: 28008555 |
Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. | Susswein LR | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26681312 |
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 |
Contribution of BRCA2 germline mutations to hereditary breast/ovarian cancer in Germany. | Hamann U | Journal of medical genetics | 2002 | PMID: 11897832 |
Variation of risks of breast and ovarian cancer associated with different germline mutations of the BRCA2 gene. | Gayther SA | Nature genetics | 1997 | PMID: 8988179 |
Mutation analysis of the BRCA2 gene in 49 site-specific breast cancer families. | Phelan CM | Nature genetics | 1996 | PMID: 8673090 |
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Text-mined citations for rs80359677 ...
HelpRecord last updated Oct 13, 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.