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NM_000059.4(BRCA2):c.9004G>A (p.Glu3002Lys) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:
Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:
Jul 7, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000031784.20

Allele description [Variation Report for NM_000059.4(BRCA2):c.9004G>A (p.Glu3002Lys)]

NM_000059.4(BRCA2):c.9004G>A (p.Glu3002Lys)

Gene:
BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q13.1
Genomic location:
Preferred name:
NM_000059.4(BRCA2):c.9004G>A (p.Glu3002Lys)
Other names:
p.E3002K:GAA>AAA
HGVS:
  • NC_000013.11:g.32379800G>A
  • NG_012772.3:g.69321G>A
  • NM_000059.4:c.9004G>AMANE SELECT
  • NP_000050.2:p.Glu3002Lys
  • NP_000050.3:p.Glu3002Lys
  • LRG_293t1:c.9004G>A
  • LRG_293:g.69321G>A
  • LRG_293p1:p.Glu3002Lys
  • NC_000013.10:g.32953937G>A
  • NM_000059.3:c.9004G>A
  • U43746.1:n.9232G>A
  • p.E3002K
Nucleotide change:
9232G>A
Protein change:
E3002K
Links:
dbSNP: rs80359152
NCBI 1000 Genomes Browser:
rs80359152
Molecular consequence:
  • NM_000059.4:c.9004G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
21

Condition(s)

Name:
Breast-ovarian cancer, familial, susceptibility to, 2 (BROVCA2)
Synonyms:
Breast-ovarian cancer, familial 2
Identifiers:
MONDO: MONDO:0012933; MedGen: C2675520; Orphanet: 145; OMIM: 612555

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000054392Sharing Clinical Reports Project (SCRP)
no assertion criteria provided
Pathogenic
(May 1, 2012)
germlineclinical testing

SCV000147510Breast Cancer Information Core (BIC) (BRCA2)
no assertion criteria provided
Uncertain significance
(Feb 20, 2004)
germlineclinical testing

SCV000267825Michigan Medical Genetics Laboratories, University of Michigan
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Apr 21, 2016)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000488701Counsyl
criteria provided, single submitter

(Counsyl Autosomal Dominant Disease Classification criteria (2015))
Likely pathogenic
(Jun 1, 2016)
unknownclinical testing

PubMed (14)
[See all records that cite these PMIDs]

Counsyl Autosomal Dominant Disease Classification criteria (2015),

Citation Link,

SCV004846104All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Jul 7, 2023)
germlineclinical testing

PubMed (20)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown4not providednot provided108544not providedclinical testing
not providedgermlineyes2not providednot providednot providednot providedclinical testing
not providedgermlinenot provided8not providednot provided8not providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
Caucasiangermlineyes2not providednot providednot providednot providedclinical testing
Western Europeangermlineyes3not providednot providednot providednot providedclinical testing
Western European, French Canadiangermlineyes2not providednot providednot providednot providedclinical testing

Citations

PubMed

Comprehensive splicing functional analysis of DNA variants of the BRCA2 gene by hybrid minigenes.

Acedo A, Sanz DJ, Durán M, Infante M, Pérez-Cabornero L, Miner C, Velasco EA.

Breast Cancer Res. 2012 May 25;14(3):R87.

PubMed [citation]
PMID:
22632462
PMCID:
PMC3446350

The BRCA2 c.9004G>A (E2002K) [corrected] variant is likely pathogenic and recurs in breast and/or ovarian cancer families of French Canadian descent.

Cote S, Arcand SL, Royer R, Nolet S, Mes-Masson AM, Ghadirian P, Foulkes WD, Tischkowitz M, Narod SA, Provencher D, Tonin PN.

Breast Cancer Res Treat. 2012 Jan;131(1):333-40. doi: 10.1007/s10549-011-1796-4. Epub 2011 Sep 27. Erratum in: Breast Cancer Res Treat. 2012 Jan;131(1):341.

PubMed [citation]
PMID:
21947752
See all PubMed Citations (27)

Details of each submission

From Sharing Clinical Reports Project (SCRP), SCV000054392.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot provided8not providednot providednot providednot providednot providednot provided

From Breast Cancer Information Core (BIC) (BRCA2), SCV000147510.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testingnot provided
2Caucasian1not providednot providedclinical testingnot provided
3Caucasian1not providednot providedclinical testingnot provided
4Western European3not providednot providedclinical testingnot provided
5Western European, French Canadian2not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided2not providednot providednot provided
2germlineyesnot providednot providednot provided1not providednot providednot provided
3germlineyesnot providednot providednot provided1not providednot providednot provided
4germlineyesnot providednot providednot provided3not providednot providednot provided
5germlineyesnot providednot providednot provided2not providednot providednot provided

From Michigan Medical Genetics Laboratories, University of Michigan, SCV000267825.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providedBloodnot providednot providednot providednot providednot provided

From Counsyl, SCV000488701.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (14)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From All of Us Research Program, National Institutes of Health, SCV004846104.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided4not providednot providedclinical testing PubMed (20)

Description

This missense variant replaces glutamic acid with lysine at codon 3002 of the BRCA2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have reported that this variant impacts BRCA1 function in homology-mediated repair assays and the rescue of Brca2-deficient mouse embryonic stem cells (PMID: 22678057, 22771033, 23108138, 29394989, 29884841, 29988080, 35736817). This variant has been detected in over 20 individuals and families affected with breast, ovarian and pancreatic cancer (PMID: 15876480, 18284688, 20694749, 22678057, 25628955, 25884701, 27223485, 27724927, 30322717, 30415210, 33471991; Leiden Open Variation Database DB-ID BRCA2_000392, 35411189, 36119527). This variant also has been reported in five families with a combined segregation likelihood ratio for pathogenicity of 30.2646 (PMID: 31131967) and is a recurrent mutation in French-Canadian hereditary breast and ovarian cancer families (PMID: 32300229). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided4not providednot providednot provided

Last Updated: Jan 19, 2025