NM_000059.4(BRCA2):c.2641G>T (p.Glu881Ter) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Oct 18, 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:: RCV000256675.7

Allele description [Variation Report for NM_000059.4(BRCA2):c.2641G>T (p.Glu881Ter)]

NM_000059.4(BRCA2):c.2641G>T (p.Glu881Ter)

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.2641G>T (p.Glu881Ter)

Other names:

2869G>T

HGVS:

NC_000013.11:g.32336996G>T
NG_012772.3:g.26517G>T
NM_000059.4:c.2641G>TMANE SELECT
NP_000050.2:p.Glu881Ter
NP_000050.3:p.Glu881Ter
LRG_293t1:c.2641G>T
LRG_293:g.26517G>T
LRG_293p1:p.Glu881Ter
NC_000013.10:g.32911133G>T
NM_000059.3:c.2641G>T
p.Glu881X

Protein change:

E881*

Links:

dbSNP: rs876658648

NCBI 1000 Genomes Browser:

rs876658648

Molecular consequence:

NM_000059.4:c.2641G>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000324093	Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	reviewed by expert panel (ENIGMA BRCA1/2 Classification Criteria (2015))	Pathogenic (Oct 18, 2016)	germline	curation	Citation Link,
SCV000326737	Consortium 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)	germline	clinical testing	CIMBA_Mutation_Classification_guidelines_May16.pdf, Citation Link,
SCV004845040	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 9, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 8988179, 11897832, 29446198, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000324093

Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)

reviewed by expert panel

(ENIGMA BRCA1/2 Classification Criteria (2015))

Pathogenic
(Oct 18, 2016)

germline

curation

Citation Link,

SCV000326737

Consortium 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)

germline

clinical testing

CIMBA_Mutation_Classification_guidelines_May16.pdf,

Citation Link,

SCV004845040

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 9, 2024)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	2	1	not provided	108544	not provided	clinical testing, curation

Citations

PubMed

Variation of risks of breast and ovarian cancer associated with different germline mutations of the BRCA2 gene.

Gayther SA, Mangion J, Russell P, Seal S, Barfoot R, Ponder BA, Stratton MR, Easton D.

Nat Genet. 1997 Jan;15(1):103-5.

PubMed [citation]

PMID:: 8988179

Contribution of BRCA2 germline mutations to hereditary breast/ovarian cancer in Germany.

Hamann U, Liu X, Lange S, Ulmer HU, Benner A, Scott RJ.

J Med Genet. 2002 Mar;39(3):E12. No abstract available.

PubMed [citation]

PMID:: 11897832
PMCID:: PMC1735066

See all PubMed Citations (4)

Details of each submission

From Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), SCV000324093.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge, SCV000326737.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	1	not provided

From All of Us Research Program, National Institutes of Health, SCV004845040.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (4)

Description

The c.2641G>T (p.Glu881*) variant in the BRCA2 gene is located on the exon 11 and introduces a premature translation termination codon (p.Glu881*), resulting in an absent or disrupted protein product. Loss-of-function variants in the BRCA2 gene are known to be pathogenic (PMID: 8988179, 11897832, 29446198). Alternative protein termination codon variants located upstream and downstream to this position in the same exon have been reported in individuals with breast and/or ovarian cancer and interpreted as pathogenic (ClinVar IDs: 51318, 9322). The variant is reported in ClinVar as pathogenic (ID: 230582) and reviewed by the expert panel. The variant is absent in the general population database (gnomAD). Therefore, the c.2641G>T (p.Glu881*) variant in the BRCA2 gene has been classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		2	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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