VCV000126178.59 - ClinVar

NM_000059.4(BRCA2):c.8487+19A>G

Germline

Top reviewed classifications are shown here.

Submission summary:

24 submissions

24 submitters

7 conditions

Reviewed by expert panel

Benign

Jan 2015 by Evidence-based…

for Breast-ovarian cancer, familial 2

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000059.4(BRCA2):c.8487+19A>G

Variation ID: 126178 Accession: VCV000126178.59

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 13q13.1 13: 32370576 (GRCh38) [ NCBI UCSC ] 13: 32944713 (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	Jan 12, 2015

HGVS

Nucleotide	Protein	Molecular consequence
NM_000059.4:c.8487+19A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NC_000013.11:g.32370576A>G
NC_000013.10:g.32944713A>G
NG_012772.3:g.60097A>G
LRG_293:g.60097A>G
LRG_293t1:c.8487+19A>G
U43746.1:n.8715+19A>G

... more HGVS ... less HGVS

Protein change

Other names

IVS19+19A>G
IVS 19+19A>G

Canonical SPDI

NC_000013.11:32370575:A:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

0.01018 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00268

Exome Aggregation Consortium (ExAC) 0.00334

1000 Genomes Project 0.01018

1000 Genomes Project 30x 0.01046

The Genome Aggregation Database (gnomAD) 0.01055

Trans-Omics for Precision Medicine (TOPMed) 0.01083

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01276

Links

Breast Cancer Information Core (BIC) (BRCA2): 8715+19&base_change=A to G ClinGen: CA025669 dbSNP: rs11571743 VarSome

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
Gene	OMIM	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	19228	19390

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.
Breast-ovarian cancer, familial, susceptibility to, 2	Benign (7)	reviewed by expert panel	Jan 12, 2015	RCV000113944.17
not specified	Benign/Likely benign (7)	criteria provided, multiple submitters, no conflicts	Aug 15, 2023	RCV000168608.35
Hereditary breast ovarian cancer syndrome	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV000206585.24
Hereditary cancer-predisposing syndrome	Benign (2)	criteria provided, multiple submitters, no conflicts	Aug 14, 2015	RCV000580360.13
Familial cancer of breast	Benign (1)	criteria provided, single submitter	Feb 23, 2017	RCV000463336.9
not provided	Benign (2)	criteria provided, multiple submitters, no conflicts	Nov 20, 2023	RCV001711374.17
Breast and/or ovarian cancer	Benign (1)	criteria provided, single submitter	Nov 18, 2022	RCV003492437.1

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.
Benign (Jan 12, 2015)	reviewed by expert panel (ENIGMA BRCA1/2 Classification Criteria (2015)) Method: curation	Breast-ovarian cancer, familial 2 Affected status: unknown Allele origin: germline	Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Accession: SCV000245177.1 First in ClinVar: Sep 29, 2015 Last updated: Sep 29, 2015	Comment: Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.04268 (African), derived from 1000 genomes (2012-04-30).
Benign (Nov 03, 2014)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: yes Allele origin: germline	Michigan Medical Genetics Laboratories, University of Michigan Accession: SCV000196014.1 First in ClinVar: Sep 29, 2015 Last updated: Sep 29, 2015	Tissue: Blood
Likely benign (Apr 25, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary breast ovarian cancer syndrome Affected status: unknown Allele origin: germline	Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. Accession: SCV000267846.1 First in ClinVar: Jan 31, 2016 Last updated: Jan 31, 2016
Benign (Aug 12, 2015)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000226860.5 First in ClinVar: Jun 28, 2015 Last updated: Sep 22, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRCA2 Number of individuals with the variant: 7 Zygosity: Single Heterozygote Sex: mixed
Benign (Feb 18, 2014)	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015)) Method: literature only	Breast-ovarian cancer, familial 2 (Autosomal dominant inheritance) Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000154073.2 First in ClinVar: Jun 09, 2014 Last updated: Dec 24, 2022	Publications: PubMed (1) PubMed: 16619214
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Hereditary breast ovarian cancer syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000262396.11 First in ClinVar: Jan 31, 2016 Last updated: Feb 28, 2024
Benign (Feb 23, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Familial cancer of breast (Autosomal dominant inheritance) Affected status: no Allele origin: germline	Baylor Genetics Accession: SCV000541049.1 First in ClinVar: Apr 17, 2017 Last updated: Apr 17, 2017
Likely benign (Jul 31, 2017)	criteria provided, single submitter (ACGS Guidelines, 2013) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Study: VKGL Data-share Consensus Accession: SCV000743346.1 First in ClinVar: Sep 29, 2015 Last updated: Sep 29, 2015
Benign (Sep 21, 2015)	criteria provided, single submitter (ACGS Guidelines, 2013) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Study: VKGL Data-share Consensus Accession: SCV000744540.1 First in ClinVar: Sep 29, 2015 Last updated: Sep 29, 2015
Benign (Dec 13, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000805781.1 First in ClinVar: May 03, 2018 Last updated: May 03, 2018
Benign (Apr 19, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) 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: SCV002025852.2 First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022	Publications: DOI: 10.3389/fgene.2022.834265 DOI: 10.3389/fgene.2022.834265 Number of individuals with the variant: 109 Geographic origin: South Africa
Benign (Feb 14, 2014)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) 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: SCV000494374.2 First in ClinVar: Feb 04, 2017 Last updated: Dec 11, 2022	Publications: PubMed (2) PubMed: 16619214‚ 22874498
Likely benign (Oct 25, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: yes Allele origin: germline	Department of Pathology and Laboratory Medicine, Sinai Health System Study: Canadian Open Genetics Repository (COGR) Accession: SCV000592199.3 First in ClinVar: Dec 06, 2016 Last updated: Dec 11, 2022
Benign (Aug 14, 2015)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV000683969.2 First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022
Benign (Mar 03, 2015)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001939396.2 First in ClinVar: Sep 29, 2021 Last updated: Mar 04, 2023
Benign (Jul 07, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: yes Allele origin: germline	KCCC/NGS Laboratory, Kuwait Cancer Control Center Accession: SCV004016839.1 First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023
Benign (Aug 15, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital Accession: SCV002551821.4 First in ClinVar: Jul 30, 2022 Last updated: Aug 18, 2023
Benign (Nov 20, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000602791.7 First in ClinVar: Dec 06, 2016 Last updated: Feb 20, 2024
Benign (Nov 19, 2014)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002677624.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Comment: This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more) This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Benign (Nov 18, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) 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: SCV004240365.1 First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024
Uncertain significance (Dec 17, 2010)	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: SCV000147376.1 First in ClinVar: Apr 04, 2014 Last updated: Apr 04, 2014	Number of individuals with the variant: 1 Geographic origin: Austria
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) Study: VKGL Data-share Consensus Accession: SCV001799145.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001906227.1 First in ClinVar: Sep 23, 2021 Last updated: Sep 23, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	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: SCV001959262.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
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Comment:

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
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
Long-range PCR and next-generation sequencing of BRCA1 and BRCA2 in breast cancer.	Ozcelik H	The Journal of molecular diagnostics : JMD	2012	PMID: 22874498
Intronic alterations in BRCA1 and BRCA2: effect on mRNA splicing fidelity and expression.	Chen X	Human mutation	2006	PMID: 16619214
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRCA2	-	-	-	-

Text-mined citations for rs11571743 ...

These 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 Jan 13, 2025

ClinVar Genomic variation as it relates to human health

NM_000059.4(BRCA2):c.8487+19A>G

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs11571743 ...