ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Pathogenic
- Review status:
- reviewed by expert panel
- Submissions:
- 7
- First in ClinVar:
- Oct 22, 2016
- Most recent Submission:
- Mar 4, 2023
- Last evaluated:
- Oct 18, 2016
- Accession:
- VCV000267050.19
- Variation ID:
- 267050
- Description:
- 1bp duplication
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NM_000059.4(BRCA2):c.8021dup (p.Ile2675fs)
- Allele ID
- 261447
- Variant type
- Duplication
- Variant length
- 1 bp
- Cytogenetic location
- 13q13.1
- Genomic location
- 13: 32363217-32363218 (GRCh38) GRCh38 UCSC
- 13: 32937354-32937355 (GRCh37) GRCh37 UCSC
- HGVS
-
Nucleotide Protein Molecular
consequenceNM_000059.4:c.8021dup MANE Select NP_000050.3:p.Ile2675fs frameshift NM_000059.3:c.8021dupA NC_000013.11:g.32363223dup NC_000013.10:g.32937360dup NG_012772.3:g.52744dup LRG_293:g.52744dup - Protein change
- I2675fs
- Other names
- 8249insA
- Canonical SPDI
- NC_000013.11:32363217:AAAAAA:AAAAAAA
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- -
- Links
- ClinGen: CA10589464
- dbSNP: rs397507952
- VarSome
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Aggregate interpretations per condition
Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
---|---|---|---|---|---|
Pathogenic | 2 | reviewed by expert panel | Oct 18, 2016 | RCV000256831.6 | |
Pathogenic | 2 | criteria provided, multiple submitters, no conflicts | Oct 6, 2020 | RCV000563722.5 | |
Pathogenic | 1 | criteria provided, single submitter | Jun 4, 2019 | RCV000482911.4 | |
Pathogenic | 1 | criteria provided, single submitter | Apr 2, 2020 | RCV001310178.2 | |
Pathogenic | 1 | criteria provided, single submitter | Nov 2, 2021 | RCV001222561.5 |
Help
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation | Variation viewer | Related variants | ||
---|---|---|---|---|---|---|
HI score Help | TS score Help | Within gene | All | |||
BRCA2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
16959 | 17098 |
Submitted interpretations and evidence
HelpInterpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
---|---|---|---|---|---|
Pathogenic
(Oct 18, 2016)
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000324614.2
First in ClinVar: Oct 22, 2016 Last updated: Feb 07, 2023 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
Pathogenic
(Apr 02, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Molecular Diagnostics, Institute of Oncology Ljubljana
Accession: SCV001499773.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
|
|
Pathogenic
(Oct 06, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV001736609.1
First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021 |
Comment:
This variant inserts 1 nucleotide in exon 18 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant inserts 1 nucleotide in exon 18 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 breast/ovarian cancer (PMID: 25203624, 29383094, 29752822). 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)
|
|
Pathogenic
(May 26, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000661432.4
First in ClinVar: Jan 01, 2018 Last updated: Nov 29, 2022 |
Comment:
The c.8021dupA pathogenic mutation, located in coding exon 17 of the BRCA2 gene, results from a duplication of A at nucleotide position 8021, causing a … (more)
The c.8021dupA pathogenic mutation, located in coding exon 17 of the BRCA2 gene, results from a duplication of A at nucleotide position 8021, causing a translational frameshift with a predicted alternate stop codon (p.I2675Dfs*6). This mutation (designated c.8015_8016insA) was identified in an individual with head and neck cancer and no family history of cancer (Meric-Bernstam F et al. Ann. Oncol. 2016 May;27:795-800). 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
|
|
Pathogenic
(Oct 02, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
|
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000327799.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
|
|
Pathogenic
(Nov 02, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001394665.4
First in ClinVar: Jul 16, 2020 Last updated: Feb 07, 2023 |
Comment:
This sequence change creates a premature translational stop signal (p.Ile2675Aspfs*6) 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.Ile2675Aspfs*6) 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 head and neck cancer and breast and/or ovarian cancer (PMID: 26787237, 29383094, 29752822, 30078507). This variant is also known as c.8016dupA or c.8015_8016insA. ClinVar contains an entry for this variant (Variation ID: 267050). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jun 04, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000565763.6
First in ClinVar: Apr 27, 2017 Last updated: Mar 04, 2023 |
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; Not … (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; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 24755471, 23047548, 26787237, 29752822, 30078507, 31825140) (less)
|
Functional evidence
HelpThere 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 this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer. | Li JY | International journal of cancer | 2019 | PMID: 29752822 |
BRCA germline mutations in an unselected nationwide cohort of Chinese patients with ovarian cancer and healthy controls. | Li A | Gynecologic oncology | 2018 | PMID: 30078507 |
Simultaneous detection of genetic and copy number alterations in BRCA1/2 genes. | Hirotsu Y | Oncotarget | 2017 | PMID: 29383094 |
Incidental germline variants in 1000 advanced cancers on a prospective somatic genomic profiling protocol. | Meric-Bernstam F | Annals of oncology : official journal of the European Society for Medical Oncology | 2016 | PMID: 26787237 |
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 |
Text-mined citations for rs397507952...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Mar 26, 2023