NM_000059.3(BRCA2):c.9117G>A (p.Pro3039=) AND Breast-ovarian cancer, familial 2

Clinical significance:Pathogenic (Last evaluated: May 25, 2017)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
10 submissions [Details]
Record status:
current
Accession:
RCV000031798.9

Allele description

NM_000059.3(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_000059.3(BRCA2):c.9117G>A (p.Pro3039=)
Other names:
p.P3039P:CCG>CCA
HGVS:
  • NC_000013.11:g.32379913G>A
  • NG_012772.3:g.69434G>A
  • NM_000059.3:c.9117G>A
  • NP_000050.2:p.Pro3039=
  • LRG_293t1:c.9117G>A
  • LRG_293:g.69434G>A
  • LRG_293p1:p.Pro3039=
  • NC_000013.10:g.32954050G>A
  • U43746.1:n.9345G>A
  • p.P3039P
Nucleotide change:
9345G>A
Protein change:
P3039P
Links:
dbSNP: rs28897756
NCBI 1000 Genomes Browser:
rs28897756
Molecular consequence:
  • NM_000059.3:c.9117G>A - synonymous variant - [Sequence Ontology: SO:0001819]
Observations:
66

Condition(s)

Name:
Breast-ovarian cancer, familial 2 (BROVCA2)
Synonyms:
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 2; BREAST CANCER, FAMILIAL, SUSCEPTIBILITY TO, 2; Breast cancer, familial 2
Identifiers:
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 providedPathogenic
(Aug 31, 2013)

History

germlineclinical testing

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

SCV000328057Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridgecriteria provided, single submitter
Pathogenic
(Oct 2, 2015)
germlineclinical testing

CIMBA_Mutation_Classification_guidelines_May16.pdf,

Citation Link,

SCV000488254Counsylcriteria provided, single submitter
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 Geneticscriteria provided, single submitter
Pathogenic
(Sep 18, 2015)
unknownclinical testing

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

SCV000605690Department of Medical Genetics,Oslo University Hospitalcriteria provided, single submitter
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 Consensusno assertion criteria providedPathogenicgermlineclinical testing

SCV000743359Genome Diagnostics Laboratory,University Medical Center Utrecht - VKGL Data-share Consensuscriteria provided, single submitter
Pathogenic
(Oct 10, 2014)
germlineclinical testing

Citation Link,

SCV000744555DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center - VKGL Data-share Consensuscriteria provided, single submitter
Pathogenic
(Sep 21, 2015)
germlineclinical testing

Citation Link,

SCV000839919Human Genome Sequencing Center Clinical Lab,Baylor College of Medicinecriteria provided, single submitter
Pathogenic
(May 25, 2017)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot provided66not providednot providednot providedclinical testing
not providedgermlinenot provided9not providednot provided9not providedclinical testing
not providedgermlineyes9not providednot providednot providednot providedclinical testing
not providednot providedyes1not 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

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, Caux-Moncoutier V, Krieger S, Barrois M, Bonnet F, Bourdon V, Bronner M, Buisson M, Coulet F, Gaildrat P, Lefol C, Léone M, Mazoyer S, Muller D, Remenieras A, Révillion F, Rouleau E, Sokolowska J, Vert JP, Lidereau R, Soubrier F, Sobol H, et al.

Hum Mutat. 2012 Aug;33(8):1228-38. doi: 10.1002/humu.22101. Epub 2012 May 11.

PubMed [citation]
PMID:
22505045

Comparative in vitro and in silico analyses of variants in splicing regions of BRCA1 and BRCA2 genes and characterization of novel pathogenic mutations.

Colombo M, De Vecchi G, Caleca L, Foglia C, Ripamonti CB, Ficarazzi F, Barile M, Varesco L, Peissel B, Manoukian S, Radice P.

PLoS One. 2013;8(2):e57173. doi: 10.1371/journal.pone.0057173. Epub 2013 Feb 22.

PubMed [citation]
PMID:
23451180
PMCID:
PMC3579815
See all PubMed Citations (6)

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, SCV000328057.3

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

From Counsyl, SCV000488254.1

#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, SCV000605690.2

#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 DNA and Cytogenetics Diagnostics Unit,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

Last Updated: Jan 4, 2020

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