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NM_000059.4(BRCA2):c.9294C>A (p.Tyr3098Ter) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:
Pathogenic (7 submissions)
Last evaluated:
Sep 8, 2016
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:
RCV000031811.20

Allele description [Variation Report for NM_000059.4(BRCA2):c.9294C>A (p.Tyr3098Ter)]

NM_000059.4(BRCA2):c.9294C>A (p.Tyr3098Ter)

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.9294C>A (p.Tyr3098Ter)
HGVS:
  • NC_000013.11:g.32394726C>A
  • NG_012772.3:g.84247C>A
  • NM_000059.4:c.9294C>AMANE SELECT
  • NP_000050.2:p.Tyr3098Ter
  • NP_000050.3:p.Tyr3098Ter
  • LRG_293t1:c.9294C>A
  • LRG_293:g.84247C>A
  • LRG_293p1:p.Tyr3098Ter
  • NC_000013.10:g.32968863C>A
  • NM_000059.3:c.9294C>A
  • U43746.1:n.9522C>A
Nucleotide change:
9522C>A
Protein change:
Y3098*
Links:
dbSNP: rs80359200
NCBI 1000 Genomes Browser:
rs80359200
Molecular consequence:
  • NM_000059.4:c.9294C>A - nonsense - [Sequence Ontology: SO:0001587]
Observations:
15

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
SCV000054419Sharing Clinical Reports Project (SCRP)
no assertion criteria provided
Pathogenic
(Oct 25, 2011)
germlineclinical testing

SCV000147603Breast Cancer Information Core (BIC) (BRCA2)
no assertion criteria provided
Pathogenic
(May 29, 2002)
germlineclinical testing

SCV000301375Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
reviewed by expert panel

(ENIGMA BRCA1/2 Classification Criteria (2015))
Pathogenic
(Sep 8, 2016)
germlinecuration

ENIGMA BRCA1/2 Classification Criteria (2015),

Citation Link,

SCV000328101Consortium 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,

SCV000786350Counsyl
criteria provided, single submitter

(Counsyl Autosomal Dominant Disease Classification criteria (2015))
Pathogenic
(Apr 16, 2018)
unknownclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Counsyl_Autosomal_Dominant_Disease_Classification_criteria_(2015)_v1.pdf,

Citation Link,

SCV000965835Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Jan 1, 2016)
inheritedclinical testing

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

SCV004047722Neuberg Centre For Genomic Medicine, NCGM
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenicgermlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot provided15not providednot providednot providedclinical testing, curation
not providedinheritedyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot provided1not providednot provided1not providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
Western European, Englishgermlineyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk.

Frank TS, Manley SA, Olopade OI, Cummings S, Garber JE, Bernhardt B, Antman K, Russo D, Wood ME, Mullineau L, Isaacs C, Peshkin B, Buys S, Venne V, Rowley PT, Loader S, Offit K, Robson M, Hampel H, Brener D, Winer EP, Clark S, et al.

J Clin Oncol. 1998 Jul;16(7):2417-25.

PubMed [citation]
PMID:
9667259

Contribution of BRCA1 and BRCA2 germ-line mutations to the incidence of breast cancer in young women: results from a prospective population-based study in France.

Bonadona V, Sinilnikova OM, Chopin S, Antoniou AC, Mignotte H, Mathevet P, Brémond A, Martin A, Bobin JY, Romestaing P, Raudrant D, Rudigoz RC, Léoné M, Chauvin F, Easton DF, Lenoir GM, Lasset C.

Genes Chromosomes Cancer. 2005 Aug;43(4):404-13.

PubMed [citation]
PMID:
15887246
See all PubMed Citations (3)

Details of each submission

From Sharing Clinical Reports Project (SCRP), SCV000054419.3

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

From Breast Cancer Information Core (BIC) (BRCA2), SCV000147603.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Western European, English1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), SCV000301375.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

Variant allele predicted to encode a truncated non-functional protein.

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

From Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge, SCV000328101.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot provided15not provided

From Counsyl, SCV000786350.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Equipe Genetique des Anomalies du Developpement, Université de Bourgogne, SCV000965835.1

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

From Neuberg Centre For Genomic Medicine, NCGM, SCV004047722.1

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

Description

The stop gained (c.9294C>A) variant has been reported previously in patients affected with Breast-ovarian cancer, familial, 2 (Lubinski et. al., 2004; Rebbeck et. al., 2018). The c.9294C>A variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic. The nucleotide change c.9294C>A in BRCA2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss-of-function variants in BRCA2 are known to be pathogenic (Borg et. al., 2010). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 24, 2024