ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.516+14C>T
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.516+14C>T
Variation ID: 132764 Accession: VCV000132764.31
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q13.1 13: 32326296 (GRCh38) [ NCBI UCSC ] 13: 32900433 (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 May 29, 2016 Aug 4, 2024 Jul 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000059.4:c.516+14C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NC_000013.11:g.32326296C>T NC_000013.10:g.32900433C>T NG_012772.3:g.15817C>T LRG_293:g.15817C>T LRG_293t1:c.516+14C>T - Protein change
- Other names
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- Canonical SPDI
- NC_000013.11:32326295:C:T
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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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0.00060 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00026
Exome Aggregation Consortium (ExAC) 0.00031
The Genome Aggregation Database (gnomAD), exomes 0.00036
Trans-Omics for Precision Medicine (TOPMed) 0.00044
1000 Genomes Project 30x 0.00047
1000 Genomes Project 0.00060
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 | ||
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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
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. |
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BRCA2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
18955 | 19114 |
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. |
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Benign (2) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000119227.27 | |
Benign (4) |
criteria provided, multiple submitters, no conflicts
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Jul 31, 2024 | RCV000179248.16 | |
Benign (1) |
criteria provided, single submitter
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Feb 23, 2017 | RCV000456351.9 | |
Benign (1) |
criteria provided, single submitter
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Apr 25, 2015 | RCV000581137.11 | |
Likely benign (1) |
criteria provided, single submitter
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May 28, 2019 | RCV000988987.9 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Oct 13, 2020 | RCV000679175.24 | |
Likely benign (1) |
criteria provided, single submitter
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Aug 9, 2022 | RCV003492513.1 |
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. |
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Benign
(Feb 23, 2017)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: no
Allele origin:
germline
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Baylor Genetics
Accession: SCV000541071.1
First in ClinVar: Apr 17, 2017 Last updated: Apr 17, 2017 |
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Benign
(Jan 27, 2014)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000167323.11
First in ClinVar: Jun 19, 2014 Last updated: May 29, 2016 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Likely benign
(Dec 30, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000805715.1
First in ClinVar: Sep 14, 2018 Last updated: Sep 14, 2018 |
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Likely benign
(May 28, 2019)
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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:
unknown
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Mendelics
Accession: SCV001138967.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Benign
(Oct 13, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002049269.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
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Benign
(Jun 20, 2016)
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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: SCV000494399.2
First in ClinVar: Jul 01, 2016 Last updated: Dec 11, 2022 |
Comment:
Variant summary: The BRCA2 c.516+14C>T variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. … (more)
Variant summary: The BRCA2 c.516+14C>T variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing, which was confirmed by multiple functional studies (Bonnet_2008, Houdayer_2012, Menendez_2012, de Garibay_2014). Although this variant has been reported in breast cancer patients, this variant was also found in 36/117190 control chromosomes, predominantly observed in the Latino subpopulation at a frequency of 0.0027521 (31/11264). This frequency is about 4 times the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503), suggesting this is likely a benign polymorphism found primarily in the populations of Latino origin. In addition, co-occurrences of this variant and a pathogenic BRCA1 variant have been reported in at least two patients (Garcia-Casado_2011 and UMD database). Furthermore, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign. (less)
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Likely benign
(Aug 09, 2022)
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criteria provided, single submitter
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV004240320.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
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Benign
(Feb 01, 2024)
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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: SCV000153972.15
First in ClinVar: Jun 03, 2014 Last updated: Feb 20, 2024 |
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Benign
(Jul 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV005090009.1
First in ClinVar: Aug 04, 2024 Last updated: Aug 04, 2024 |
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Benign
(Dec 04, 2014)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000231468.5
First in ClinVar: Jun 28, 2015 Last updated: May 29, 2016 |
Number of individuals with the variant: 1
Sex: mixed
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Benign
(Apr 25, 2015)
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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: SCV000683678.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591688.2 First in ClinVar: May 29, 2016 Last updated: Apr 13, 2021 |
Comment:
The BRCA2 c.516+14C>T variant has been shown not to impact mRNA splicing in in vitro splicing assays (Bonnet 2008, Houdayer2012). The variant was identified in … (more)
The BRCA2 c.516+14C>T variant has been shown not to impact mRNA splicing in in vitro splicing assays (Bonnet 2008, Houdayer2012). The variant was identified in dbSNP (ID: rs rs182828913) “With benign allele”, with a minor allele frequency of .0006/3 (1000 Genomes Project, in 3 of 5000 chromosomes, frequency 0.0006), the Exome Aggregation Consortium (ExAC) database (released Oct 20th, 2014) in 36 of 116930 chromosomes (frequency: 0.0003) (or 5 individuals from a population of 63686 European (Non-Finnish) individuals, 31 of 11264 Latino individuals, and none from East Asian, Other, African, South Asian or European (Finnish) individuals; Clinvitae database (2X as benign/likely benign), the ClinVar database (classified as a benign variant by Invitae and GeneDX), GeneInsight COGR database (1X, unclassified by a clinical laboratory), and UMD (12X as a likely neutral variant, with a co-occurring pathogenic BRCA1 variant (c.-200_80del (p.Met1SerfsX13)), increasing the likelihood that the c.516+14C>T variant does not have clinical significance. The variant was also identified by our laboratory in 1 individual with breast cancer. The variant occurs outside of the splicing consensus sequence and 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 laboratory's criteria to be classified as benign. (less)
Number of individuals with the variant: 9
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001955515.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001973566.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001927954.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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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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Capillary electrophoresis analysis of conventional splicing assays: IARC analytical and clinical classification of 31 BRCA2 genetic variants. | de Garibay GR | Human mutation | 2014 | PMID: 24123850 |
Functional and structural analysis of C-terminal BRCA1 missense variants. | Quiles F | PloS one | 2013 | PMID: 23613828 |
Prevalance of BRCA1 and BRCA2 mutations in familial breast cancer patients in Lebanon. | Jalkh N | Hereditary cancer in clinical practice | 2012 | PMID: 22713736 |
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 |
Assessing the RNA effect of 26 DNA variants in the BRCA1 and BRCA2 genes. | Menéndez M | Breast cancer research and treatment | 2012 | PMID: 21735045 |
A de novo complete BRCA1 gene deletion identified in a Spanish woman with early bilateral breast cancer. | Garcia-Casado Z | BMC medical genetics | 2011 | PMID: 21989022 |
Screening BRCA1 and BRCA2 unclassified variants for splicing mutations using reverse transcription PCR on patient RNA and an ex vivo assay based on a splicing reporter minigene. | Bonnet C | Journal of medical genetics | 2008 | PMID: 18424508 |
Differences in the frequency and distribution of BRCA1 and BRCA2 mutations in breast/ovarian cancer cases from the Basque country with respect to the Spanish population: implications for genetic counselling. | Beristain E | Breast cancer research and treatment | 2007 | PMID: 17262179 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRCA2 | - | - | - | - |
Text-mined citations for rs182828913 ...
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.