NM_000059.4(BRCA2):c.2786dup (p.Leu929fs) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Pathogenic (5 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:: RCV000077694.17

Allele description [Variation Report for NM_000059.4(BRCA2):c.2786dup (p.Leu929fs)]

NM_000059.4(BRCA2):c.2786dup (p.Leu929fs)

Gene:

BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.2786dup (p.Leu929fs)

Other names:

3014insT

HGVS:

NC_000013.11:g.32337141dup
NG_012772.3:g.26662dup
NM_000059.4:c.2786dupMANE SELECT
NM_000059.4:c.2786dupT
NP_000050.3:p.Leu929fs
LRG_293t1:c.2786dup
LRG_293:g.26662dup
NC_000013.10:g.32911274_32911275insT
NC_000013.10:g.32911278dup
NM_000059.3:c.2786dup
NM_000059.3:c.2786dupT
U43746.1:n.3014_3015insT

Nucleotide change:

3014INST

Protein change:

L929fs

Links:

Breast Cancer Information Core (BIC) (BRCA2): 3014&base_change=ins T; dbSNP: rs80359347

NCBI 1000 Genomes Browser:

rs80359347

Molecular consequence:

NM_000059.4:c.2786dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000109497	Sharing Clinical Reports Project (SCRP)	no assertion criteria provided	Pathogenic (Jul 24, 2008)	germline	clinical testing
SCV000146108	Breast Cancer Information Core (BIC) (BRCA2)	no assertion criteria provided	Pathogenic (Feb 20, 2004)	germline	clinical testing
SCV000300555	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,
SCV000326766	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,
SCV004845056	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 8, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15131399, 24549055, 29446198, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	5	not provided	108544	not provided	clinical testing, curation
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	1	not provided	not provided	1	not provided	clinical testing
Caucasian	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Western European	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Cancer variation associated with the position of the mutation in the BRCA2 gene.

Lubinski J, Phelan CM, Ghadirian P, Lynch HT, Garber J, Weber B, Tung N, Horsman D, Isaacs C, Monteiro AN, Sun P, Narod SA.

Fam Cancer. 2004;3(1):1-10.

PubMed [citation]

PMID:: 15131399

Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes.

Castéra L, Krieger S, Rousselin A, Legros A, Baumann JJ, Bruet O, Brault B, Fouillet R, Goardon N, Letac O, Baert-Desurmont S, Tinat J, Bera O, Dugast C, Berthet P, Polycarpe F, Layet V, Hardouin A, Frébourg T, Vaur D.

Eur J Hum Genet. 2014 Nov;22(11):1305-13. doi: 10.1038/ejhg.2014.16. Epub 2014 Feb 19.

PubMed [citation]

PMID:: 24549055
PMCID:: PMC4200427

See all PubMed Citations (4)

Details of each submission

From Sharing Clinical Reports Project (SCRP), SCV000109497.2

#	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	1	not provided	not provided		not provided	not provided	not provided	not provided

From Breast Cancer Information Core (BIC) (BRCA2), SCV000146108.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided
2	Caucasian	1	not provided	not provided	clinical testing	not provided
3	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
3	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), SCV000300555.2

#	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, SCV000326766.4

#	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	5	not provided

From All of Us Research Program, National Institutes of Health, SCV004845056.1

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

Description

This variant inserts 1 nucleotide in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals with a personal or family history of breast and/or ovarian cancer (PMID: 15131399, 24549055, 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: Oct 26, 2024

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