NM_000059.4(BRCA2):c.2517C>A (p.Tyr839Ter) 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:: RCV000113053.15

Allele description [Variation Report for NM_000059.4(BRCA2):c.2517C>A (p.Tyr839Ter)]

NM_000059.4(BRCA2):c.2517C>A (p.Tyr839Ter)

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.2517C>A (p.Tyr839Ter)

HGVS:

NC_000013.11:g.32336872C>A
NG_012772.3:g.26393C>A
NM_000059.4:c.2517C>AMANE SELECT
NP_000050.2:p.Tyr839Ter
NP_000050.3:p.Tyr839Ter
LRG_293t1:c.2517C>A
LRG_293:g.26393C>A
LRG_293p1:p.Tyr839Ter
NC_000013.10:g.32911009C>A
NM_000059.3:c.2517C>A
U43746.1:n.2745C>A
p.Y839*

Protein change:

Y839*

Links:

dbSNP: rs80358516

NCBI 1000 Genomes Browser:

rs80358516

Molecular consequence:

NM_000059.4:c.2517C>A - 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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TRPV3 transient receptor potential cation channel subfamily V member 3 [Homo sap...
TRPV3 transient receptor potential cation channel subfamily V member 3 [Homo sapiens]
Gene ID:162514

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Gene for MedGen (Select 1778121) (1)
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RETREG1 reticulophagy regulator 1 [Homo sapiens]
RETREG1 reticulophagy regulator 1 [Homo sapiens]
Gene ID:54463

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Gene for MedGen (Select 413474) (1)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000146060	Breast Cancer Information Core (BIC) (BRCA2)	no assertion criteria provided	Pathogenic (Jun 12, 2000)	germline	clinical testing
SCV000300526	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,
SCV000326719	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,
SCV004847064	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 13, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28152038, 29446198, 25741868

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Summary from all submissions

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

Citations

PubMed

Exome sequencing covers >98% of mutations identified on targeted next generation sequencing panels.

LaDuca H, Farwell KD, Vuong H, Lu HM, Mu W, Shahmirzadi L, Tang S, Chen J, Bhide S, Chao EC.

PLoS One. 2017;12(2):e0170843. doi: 10.1371/journal.pone.0170843.

PubMed [citation]

PMID:: 28152038
PMCID:: PMC5289469

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

Rebbeck TR, Friebel TM, Friedman E, Hamann U, Huo D, Kwong A, Olah E, Olopade OI, Solano AR, Teo SH, Thomassen M, Weitzel JN, Chan TL, Couch FJ, Goldgar DE, Kruse TA, Palmero EI, Park SK, Torres D, van Rensburg EJ, McGuffog L, Parsons MT, et al.

Hum Mutat. 2018 May;39(5):593-620. doi: 10.1002/humu.23406. Epub 2018 Mar 12.

PubMed [citation]

PMID:: 29446198
PMCID:: PMC5903938

See all PubMed Citations (3)

Details of each submission

From Breast Cancer Information Core (BIC) (BRCA2), SCV000146060.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided
2	Western European	1	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	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
2	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), SCV000300526.2

#	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, SCV000326719.4

#	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, SCV004847064.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)

Description

This variant changes 1 nucleotide in exon 11 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 detected in families suspected of having hereditary breast and ovarian cancer (PMID: 28152038, 29446198). 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: Nov 10, 2024

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