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NM_000059.4(BRCA2):c.9117G>A (p.Pro3039=) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:
Pathogenic (14 submissions)
Last evaluated:
Nov 9, 2023
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV000031798.30

Allele description [Variation Report for NM_000059.4(BRCA2):c.9117G>A (p.Pro3039=)]

NM_000059.4(BRCA2):c.9117G>A (p.Pro3039=)

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.9117G>A (p.Pro3039=)
Other names:
P3039P; p.P3039P:CCG>CCA; NM_000059.4(BRCA2):c.9117G>A; p.Pro3039=
HGVS:
  • NC_000013.11:g.32379913G>A
  • NG_012772.3:g.69434G>A
  • NM_000059.4:c.9117G>AMANE SELECT
  • NP_000050.2:p.Pro3039=
  • NP_000050.3:p.Pro3039=
  • LRG_293t1:c.9117G>A
  • LRG_293:g.69434G>A
  • LRG_293p1:p.Pro3039=
  • NC_000013.10:g.32954050G>A
  • NM_000059.3:c.9117G>A
  • U43746.1:n.9345G>A
  • p.P3039P
Nucleotide change:
9345G>A
Links:
dbSNP: rs28897756
NCBI 1000 Genomes Browser:
rs28897756
Molecular consequence:
  • NM_000059.4:c.9117G>A - synonymous variant - [Sequence Ontology: SO:0001819]
Observations:
67

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
SCV000054406Sharing Clinical Reports Project (SCRP)
no assertion criteria provided
Pathogenic
(Aug 31, 2013)
germlineclinical testing

SCV000147546Breast Cancer Information Core (BIC) (BRCA2)
no assertion criteria provided
Pathogenic
(Feb 20, 2004)
germline, unknownclinical testing

SCV000328057Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
criteria provided, single submitter

(CIMBA Mutation Classification guidelines May 2016)
Pathogenic
(Oct 2, 2015)
germlineclinical testing

CIMBA_Mutation_Classification_guidelines_May16.pdf,

Citation Link,

SCV000488254Counsyl
criteria provided, single submitter

(Counsyl Autosomal Dominant Disease Classification criteria (2015))
Pathogenic
(Feb 3, 2016)
unknownclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Counsyl Autosomal Dominant Disease Classification criteria (2015),

Citation Link,

SCV000575743Fulgent Genetics, Fulgent Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Sep 18, 2015)
unknownclinical testing

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

SCV000605690Department of Medical Genetics, Oslo University Hospital
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Nov 2, 2015)
germlineclinical testing

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

SCV000733331Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus
no assertion criteria provided
Pathogenicgermlineclinical testing

SCV000743359Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus
criteria provided, single submitter

(ACGS Guidelines, 2013)
Pathogenic
(Oct 10, 2014)
germlineclinical testing

Citation Link,

SCV000744555Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus
criteria provided, single submitter

(ACGS Guidelines, 2013)
Pathogenic
(Sep 21, 2015)
germlineclinical testing

Citation Link,

SCV000839919Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(May 25, 2017)
germlineclinical testing

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

SCV001139248Mendelics
criteria provided, single submitter

(Mendelics Assertion Criteria 2017)
Pathogenic
(May 28, 2019)
unknownclinical testing

Citation Link,

SCV001251960Genomic Research Center, Shahid Beheshti University of Medical Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(May 3, 2020)
unknownclinical testing

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

SCV002588935BRCAlab, Lund University
no assertion criteria provided
Pathogenic
(Aug 26, 2022)
germlineclinical testing

SCV004846127All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Nov 9, 2023)
germlineclinical testing

PubMed (19)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided9not providednot provided9not providedclinical testing
not providedgermlineunknown466not provided108544not providedclinical testing
not providedgermlineyes91not providednot providednot providedclinical testing
not providednot providedyes1not providednot providednot providednot providedclinical testing
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
Africangermlineyes2not providednot providednot providednot providedclinical testing
Ashkenazigermlineyes1not providednot providednot providednot providedclinical testing
Caucasiangermlineyes1not providednot providednot providednot providedclinical testing
Western Europeangermlineyes4not providednot providednot providednot providedclinical testing
Western European, Italiangermlineyes1not 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

Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer.

Zhang S, Royer R, Li S, McLaughlin JR, Rosen B, Risch HA, Fan I, Bradley L, Shaw PA, Narod SA.

Gynecol Oncol. 2011 May 1;121(2):353-7. doi: 10.1016/j.ygyno.2011.01.020. Epub 2011 Feb 15.

PubMed [citation]
PMID:
21324516
See all PubMed Citations (22)

Details of each submission

From Sharing Clinical Reports Project (SCRP), SCV000054406.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot provided9not providednot providednot providednot providednot providednot provided

From Breast Cancer Information Core (BIC) (BRCA2), SCV000147546.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided4not providednot providedclinical testingnot provided
2not provided1not providednot providedclinical testingnot provided
3African2not providednot providedclinical testingnot provided
4Ashkenazi1not providednot providedclinical testingnot provided
5Caucasian1not providednot providedclinical testingnot provided
6Western European4not providednot providedclinical testingnot provided
7Western European, Italian1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided4not providednot providednot provided
2unknownyesnot providednot providednot provided1not providednot providednot provided
3germlineyesnot providednot providednot provided2not providednot providednot provided
4germlineyesnot providednot providednot provided1not providednot providednot provided
5germlineyesnot providednot providednot provided1not providednot providednot provided
6germlineyesnot providednot providednot provided4not providednot providednot provided
7germlineyesnot providednot providednot provided1not providednot providednot provided

From Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge, SCV000328057.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot provided66not provided

From Counsyl, SCV000488254.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Fulgent Genetics, Fulgent Genetics, SCV000575743.1

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

From Department of Medical Genetics, Oslo University Hospital, SCV000605690.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided5not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided5not providednot providednot provided

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV000733331.1

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

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV000743359.1

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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV000744555.1

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

From Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine, SCV000839919.1

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

Description

The c.9117G>A (p.Pro3039Pro) variant in the BRCA2 gene has been detected in multiple patients and families with breast and/or ovarian cancer [PMID 10638982 reported as 3398delAAAAG, 27000661] and a cohort of patients with prostate cancer [PMID 23035815, reported as c.9117 G>A (p.Val2985fs)]. The nucleotide position 9117 is the last nucleotide of exon 23. Several in vitro assays showed that the change leads aberrant splicing and the skipping of exon 23 [PMID 22505045, 23451180]. This variant is thus predicted to result in a loss of function of the protein. This variant has not been reported in the ExAC database. This variant thus classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Mendelics, SCV001139248.1

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

From Genomic Research Center, Shahid Beheshti University of Medical Sciences, SCV001251960.1

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

From BRCAlab, Lund University, SCV002588935.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot provided1not provided

From All of Us Research Program, National Institutes of Health, SCV004846127.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided4not providednot providedclinical testing PubMed (19)

Description

This variant changes a conserved and the last nucleotide in exon 23, and it is predicted to disrupt the intron 23 splice donor site. RNA studies have shown that this variant impacts splicing resulting in exon 23 skipping and introducing premature stop (PMID: 22505045, 23451180, 25382762, 27060066, 31843900, 32393398). This variant is expected to result in an absent or non-functional protein product. This variant has been reported in at least 10 individuals affected with breast or ovarian cancer (PMID: 18821011, 22798144, 24156927, 24249303, 25480878, 25556971, 25948282, 26026974, 27000661, 28477318, 28724667, 30287823). This variant has been identified in 1/248378 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

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

Last Updated: Nov 3, 2024