NM_000059.4(BRCA2):c.8839G>T (p.Glu2947Ter) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Pathogenic (4 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:: RCV000077644.8

Allele description [Variation Report for NM_000059.4(BRCA2):c.8839G>T (p.Glu2947Ter)]

NM_000059.4(BRCA2):c.8839G>T (p.Glu2947Ter)

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.8839G>T (p.Glu2947Ter)

HGVS:

NC_000013.11:g.32379401G>T
NG_012772.3:g.68922G>T
NM_000059.4:c.8839G>TMANE SELECT
NP_000050.2:p.Glu2947Ter
NP_000050.3:p.Glu2947Ter
LRG_293t1:c.8839G>T
LRG_293:g.68922G>T
LRG_293p1:p.Glu2947Ter
NC_000013.10:g.32953538G>T
NM_000059.3:c.8839G>T

Nucleotide change:

9067G>T

Protein change:

E2947*

Links:

dbSNP: rs398122715

NCBI 1000 Genomes Browser:

rs398122715

Molecular consequence:

NM_000059.4:c.8839G>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
SCV000109447	Sharing Clinical Reports Project (SCRP)	no assertion criteria provided	Pathogenic (Aug 10, 2010)	germline	clinical testing
SCV000301314	Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	reviewed by expert panel (ENIGMA BRCA1/2 Classification Criteria (2015))	Pathogenic (Sep 8, 2016)	germline	curation	ENIGMA BRCA1/2 Classification Criteria (2015), Citation Link,
SCV000327975	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,
SCV004846080	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 15, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31921681, 25741868

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Summary from all submissions

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

Citations

PubMed

Latin American Study of Hereditary Breast and Ovarian Cancer LACAM: A Genomic Epidemiology Approach.

Oliver J, Quezada Urban R, Franco Cortés CA, Díaz Velásquez CE, Montealegre Paez AL, Pacheco-Orozco RA, Castro Rojas C, García-Robles R, López Rivera JJ, Gaitán Chaparro S, Gómez AM, Suarez Obando F, Giraldo G, Maya MI, Hurtado-Villa P, Sanchez AI, Serrano N, Orduz Galvis AI, Aruachan S, Nuñez Castillo J, Frecha C, Riggi C, et al.

Front Oncol. 2019;9:1429. doi: 10.3389/fonc.2019.01429.

PubMed [citation]

PMID:: 31921681
PMCID:: PMC6933010

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Sharing Clinical Reports Project (SCRP), SCV000109447.3

#	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	not provided	2	not provided	not provided		not provided	not provided	not provided	not provided

From Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), SCV000301314.2

#	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, SCV000327975.4

#	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	2	not provided

From All of Us Research Program, National Institutes of Health, SCV004846080.1

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

Description

This variant changes 1 nucleotide in exon 22 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual at high-risk of hereditary breast and ovarian cancer (PMID: 31921681). This variant has not been identified 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.

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

Last Updated: Sep 29, 2024

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