ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.7805+6C>G
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.7805+6C>G
Variation ID: 52412 Accession: VCV000052412.68
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 13q13.1 13: 32357935 (GRCh38) [ NCBI UCSC ] 13: 32932072 (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 1, 2014 Feb 20, 2024 Feb 1, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000059.4:c.7805+6C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NC_000013.11:g.32357935C>G NC_000013.10:g.32932072C>G NG_012772.3:g.47456C>G LRG_293:g.47456C>G LRG_293t1:c.7805+6C>G U43746.1:n.8033+6C>G - Protein change
- Other names
- IVS16+6C>G
- Canonical SPDI
- NC_000013.11:32357934:C:G
-
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.
-
0.00160 (G)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00063
Exome Aggregation Consortium (ExAC) 0.00072
1000 Genomes Project 0.00160
1000 Genomes Project 30x 0.00172
The Genome Aggregation Database (gnomAD) 0.00290
Trans-Omics for Precision Medicine (TOPMed) 0.00293
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00331
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 |
18776 | 18934 |
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. |
---|---|---|---|---|
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000045315.21 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Apr 21, 2016 | RCV000077412.11 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Oct 27, 2020 | RCV000174984.19 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Jul 8, 2020 | RCV000580581.4 | |
Likely benign (1) |
criteria provided, single submitter
|
May 4, 2022 | RCV003149691.2 | |
Benign (1) |
criteria provided, single submitter
|
Nov 29, 2023 | RCV003103725.4 |
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. |
|
---|---|---|---|---|---|
Benign
(Mar 20, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000805768.1
First in ClinVar: Aug 27, 2017 Last updated: Aug 27, 2017 |
|
|
Benign
(Aug 04, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000226399.5
First in ClinVar: Jun 28, 2015 Last updated: Aug 27, 2017 |
Number of individuals with the variant: 1
Sex: mixed
|
|
Benign
(Mar 28, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000494369.2
First in ClinVar: Feb 04, 2017 Last updated: Dec 11, 2022 |
|
|
Benign
(Apr 21, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
Michigan Medical Genetics Laboratories, University of Michigan
Accession: SCV000267810.1
First in ClinVar: May 27, 2015 Last updated: May 27, 2015 |
Tissue: Blood
|
|
Likely benign
(Oct 27, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002070583.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
|
|
Benign
(Apr 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Accession: SCV002025829.2
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 20
Geographic origin: South Africa
|
|
Likely benign
(Nov 01, 2021)
|
criteria provided, single submitter
Method: research
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
Genetics Program, Instituto Nacional de Cancer
Accession: SCV002515149.1
First in ClinVar: Nov 19, 2022 Last updated: Nov 19, 2022 |
Geographic origin: Brazil
|
|
Benign
(Mar 08, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000683909.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
|
|
Likely benign
(Mar 18, 2014)
|
criteria provided, single submitter
Method: literature only
|
Breast-ovarian cancer, familial 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000154087.2
First in ClinVar: Jun 09, 2014 Last updated: Dec 24, 2022 |
|
|
Likely benign
(May 04, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV003838177.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000073328.15
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
|
|
Benign
(Nov 29, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602796.5
First in ClinVar: Aug 27, 2017 Last updated: Feb 20, 2024 |
|
|
Benign
(Jul 08, 2020)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002531884.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000592144.2 First in ClinVar: Aug 27, 2017 Last updated: Feb 09, 2020 |
Comment:
The c.7805+6C>G variant was shown to produce a wildtype transcript in an m RNA based assay using lymphocyte cell lines of variant carriers, who met … (more)
The c.7805+6C>G variant was shown to produce a wildtype transcript in an m RNA based assay using lymphocyte cell lines of variant carriers, who met requirements for clinical testing or research into familial aspects of breast cancer; with aberrant in vitro transcripts accurately predicted by splice prediction programs (Whiley 2011). The variant was also identified in dbSNP (ID: rs81002819) “With other allele”, with a minor allele frequency of 0.001 (1000 Genomes Project), and the BIC database (19X with unknown clinical importance). The variant was identified by the Exome Variant Server project in 43 of 4406 African American alleles (frequency: 0.01). The variant was identified in UMD (12X as an unclassified variant) with co-occurring pathogenic variants: BRCA1 c.3607C>T (p.Arg1203X), BRCA2 c.7679_7680delTT (p.Phe2560SerfsX5), and BRCA2 c.2627delA (p.Asn876IlefsX19, increasing the likelihood that the c.7805+6C>G variant does not have clinical significance. The variant was also identified by the Sharing Clinical Reports Project (SCRP) (submitted within the ClinVar database and derived from Myriad reports) 2X (1X by multiple submitters (SCRP as benign, and BIC as uncertain) and 1X by Invitae, classification not provided). The c.7805+6C>G variant is located in the 5' splice region but does not affect the invariant +1 and +2 positions. However, positions +3 to +6 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. In silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, this variant meets our laboratoy’s criteria to be classified as benign. (less)
Number of individuals with the variant: 3
|
|
Uncertain significance
(May 29, 2002)
|
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: SCV000147186.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 4
Observation 2:
Number of individuals with the variant: 1
Geographic origin: Latin American, Caribbean
Observation 3:
Number of individuals with the variant: 7
Ethnicity/Population group: African
Observation 4:
Number of individuals with the variant: 2
Ethnicity/Population group: African American
Observation 5:
Number of individuals with the variant: 1
Ethnicity/Population group: African, Latin American, Caribbean
Observation 6:
Number of individuals with the variant: 4
Ethnicity/Population group: Latin American, Caribbean
|
|
Benign
(May 01, 2012)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 2
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000109210.5
First in ClinVar: Dec 23, 2013 Last updated: May 27, 2015 |
|
|
click to load more click to collapse |
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 |
---|---|---|---|---|
Familial history and prevalence of BRCA1, BRCA2 and TP53 pathogenic variants in HBOC Brazilian patients from a public healthcare service. | Matta BP | Scientific reports | 2022 | PMID: 36329109 |
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 |
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 |
Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants. | Houdayer C | Human mutation | 2012 | PMID: 22505045 |
Mutation screening of RAD51C in high-risk breast and ovarian cancer families. | Lu W | Familial cancer | 2012 | PMID: 22476429 |
High prevalence of BRCA1 and BRCA2 mutations in unselected Nigerian breast cancer patients. | Fackenthal JD | International journal of cancer | 2012 | PMID: 22034289 |
Splicing and multifactorial analysis of intronic BRCA1 and BRCA2 sequence variants identifies clinically significant splicing aberrations up to 12 nucleotides from the intron/exon boundary. | Whiley PJ | Human mutation | 2011 | PMID: 21394826 |
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 |
The relative contribution of point mutations and genomic rearrangements in BRCA1 and BRCA2 in high-risk breast cancer families. | Palma MD | Cancer research | 2008 | PMID: 18703817 |
Evaluation of unclassified variants in the breast cancer susceptibility genes BRCA1 and BRCA2 using five methods: results from a population-based study of young breast cancer patients. | Lee E | Breast cancer research : BCR | 2008 | PMID: 18284688 |
The breast cancer information core: database design, structure, and scope. | Szabo C | Human mutation | 2000 | PMID: 10923033 |
Incidence of BRCA1/2 germ line alterations in a high risk cohort participating in a phase II chemoprevention trial. | Klemp J | European journal of cancer (Oxford, England : 1990) | 2000 | PMID: 10882858 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRCA2 | - | - | - | - |
click to load more click to collapse |
Text-mined citations for rs81002819 ...
HelpRecord last updated Jul 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.