ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.6129dup (p.Gly2044fs)
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
-
NM_000059.4(BRCA2):c.6129dup (p.Gly2044fs)
Variation ID: 52018 Accession: VCV000052018.14
- Type and length
-
Duplication, 1 bp
- Location
-
Cytogenetic: 13q13.1 13: 32340479-32340480 (GRCh38) [ NCBI UCSC ] 13: 32914616-32914617 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 4, 2014 May 1, 2024 Sep 8, 2016 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000059.4:c.6129dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Gly2044fs frameshift NM_000059.3:c.6129dupA NC_000013.11:g.32340484dup NC_000013.10:g.32914621dup NG_012772.3:g.30005dup LRG_293:g.30005dup U43746.1:n.6357_6358insA - Protein change
- G2044fs
- Other names
- 6357insA
- Canonical SPDI
- NC_000013.11:32340479:AAAAA:AAAAAA
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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. |
|||
BRCA2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
18723 | 18881 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (3) |
reviewed by expert panel
|
Sep 8, 2016 | RCV000113535.6 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
May 16, 2016 | RCV000481411.3 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jul 9, 2017 | RCV001382369.6 | |
Pathogenic (1) |
criteria provided, single submitter
|
Feb 5, 2020 | RCV002354238.2 |
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
Help
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
Help
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
Help
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. |
|
---|---|---|---|---|---|
Pathogenic
(Sep 08, 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: SCV000300986.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
Pathogenic
(May 16, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000568473.4
First in ClinVar: Apr 27, 2017 Last updated: Sep 28, 2017 |
Comment:
This duplication of one nucleotide in BRCA2 is denoted c.6129dupA at the cDNA level and p.Gly2044ArgfsX5 (G2044RfsX5) at the protein level. The normal sequence, with … (more)
This duplication of one nucleotide in BRCA2 is denoted c.6129dupA at the cDNA level and p.Gly2044ArgfsX5 (G2044RfsX5) at the protein level. The normal sequence, with the base that is duplicated in braces, is CAAAA[A]GGCT. The duplication causes a frameshift which changes a Glycine to an Arginine at codon 2044, and creates a premature stop codon at position 5 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.6129dupA, also known as BRCA2 6357dupA by alternate nomenclature, has been identified in an individual undergoing testing for Hereditary Breast and Ovarian Cancer (Frank 2002, Phelan 2002). We consider this variant to be pathogenic. (less)
|
|
Pathogenic
(Apr 09, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296542.3
First in ClinVar: Apr 04, 2014 Last updated: Jan 01, 2022 |
|
|
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: SCV000327359.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
|
|
Pathogenic
(Feb 05, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002661300.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.6129dupA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a duplication of A at nucleotide position 6129, causing a … (more)
The c.6129dupA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a duplication of A at nucleotide position 6129, causing a translational frameshift with a predicted alternate stop codon (p.G2044Rfs*5). This alteration has been identified in multiple patients referred for evaluation due to personal and/or family history of breast and/or ovarian cancer and was identified in a large, worldwide study of BRCA1/2 mutation positive families (Finkelman BS et al. J. Clin. Oncol., 2012 Apr;30:1321-8; Carter NJ et al. Gynecol. Oncol., 2018 12;151:481-488; Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620). Of note, this alteration is also designated as 6357insA 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)
|
|
Pathogenic
(Jul 09, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001581117.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant has been … (more)
For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant has been reported in multiple individuals affected with breast and/or ovarian cancer (PMID: 12402332, 22430266). This variant is also known as 6357insA in the literature. ClinVar contains an entry for this variant (Variation ID: 52018). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gly2044Argfs*5) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. (less)
|
|
Pathogenic
(Jan 17, 2001)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 2
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000146774.1
First in ClinVar: Apr 04, 2014 Last updated: Apr 04, 2014 |
Number of individuals with the variant: 1
Ethnicity/Population group: Ashkenazi
|
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 |
---|---|---|---|---|
Germline pathogenic variants identified in women with ovarian tumors. | Carter NJ | Gynecologic oncology | 2018 | PMID: 30322717 |
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
Breast and ovarian cancer risk and risk reduction in Jewish BRCA1/2 mutation carriers. | Finkelman BS | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2012 | PMID: 22430266 |
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 |
A low frequency of non-founder BRCA1 mutations in Ashkenazi Jewish breast-ovarian cancer families. | Phelan CM | Human mutation | 2002 | PMID: 12402332 |
Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. | Frank TS | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2002 | PMID: 11896095 |
Text-mined citations for rs80359561 ...
HelpRecord last updated May 01, 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.