NM_000059.4(BRCA2):c.2957dup (p.Asn986fs) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Pathogenic (6 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:: RCV000077700.19

Allele description [Variation Report for NM_000059.4(BRCA2):c.2957dup (p.Asn986fs)]

NM_000059.4(BRCA2):c.2957dup (p.Asn986fs)

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.2957dup (p.Asn986fs)

HGVS:

NC_000013.11:g.32337312dup
NG_012772.3:g.26833dup
NM_000059.4:c.2957dupMANE SELECT
NM_000059.4:c.2957dupA
NP_000050.3:p.Asn986fs
LRG_293t1:c.2957dup
LRG_293:g.26833dup
NC_000013.10:g.32911442_32911443insA
NC_000013.10:g.32911449dup
NM_000059.3:c.2951dupA
NM_000059.3:c.2957dup
NM_000059.3:c.2957dupA
NM_000059.4:c.2957dup
U43746.1:n.3185_3186insA
p.Asn986Lysfs*2
p.N986KfsX2

Nucleotide change:

3185insA

Protein change:

N986fs

Links:

Breast Cancer Information Core (BIC) (BRCA2): 3185&base_change=ins A; dbSNP: rs80359365

NCBI 1000 Genomes Browser:

rs80359365

Molecular consequence:

NM_000059.4:c.2957dup - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000109503	Sharing Clinical Reports Project (SCRP)	no assertion criteria provided	Pathogenic (Feb 25, 2011)	germline	clinical testing
SCV000146148	Breast Cancer Information Core (BIC) (BRCA2)	no assertion criteria provided	Pathogenic (Jun 20, 2002)	germline	clinical testing
SCV000300575	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,
SCV000326792	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,
SCV004242473	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 10, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004845086	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 19, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 16683254, 24156927, 26219728, 29446198, 32918181, 33471991, 25741868

Help

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	not provided	3	not provided	not provided	3	not provided	clinical testing
not provided	germline	unknown	1	7	not provided	108544	not provided	clinical testing, curation
not provided	unknown	yes	not provided	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

A DGGE system for comprehensive mutation screening of BRCA1 and BRCA2: application in a Dutch cancer clinic setting.

van der Hout AH, van den Ouweland AM, van der Luijt RB, Gille HJ, Bodmer D, Brüggenwirth H, Mulder IM, van der Vlies P, Elfferich P, Huisman MT, ten Berge AM, Kromosoeto J, Jansen RP, van Zon PH, Vriesman T, Arts N, Lange MB, Oosterwijk JC, Meijers-Heijboer H, Ausems MG, Hoogerbrugge N, Verhoef S, et al.

Hum Mutat. 2006 Jul;27(7):654-66.

PubMed [citation]

PMID:: 16683254

Central European BRCA2 mutation carriers: birth cohort status correlates with onset of breast cancer.

Tea MK, Kroiss R, Muhr D, Fuerhauser-Rappaport C, Oefner P, Wagner TM, Singer CF.

Maturitas. 2014 Jan;77(1):68-72. doi: 10.1016/j.maturitas.2013.09.012. Epub 2013 Oct 1.

PubMed [citation]

PMID:: 24156927

See all PubMed Citations (7)

Details of each submission

From Sharing Clinical Reports Project (SCRP), SCV000109503.3

#	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	3	not provided	not provided		not provided	not provided	not provided	not provided

From Breast Cancer Information Core (BIC) (BRCA2), SCV000146148.1

#	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), SCV000300575.2

#	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, SCV000326792.4

#	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	7	not provided

From Institute of Human Genetics, University of Leipzig Medical Center, SCV004242473.2

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

Description

Criteria applied: PVS1,PS4_MOD,PM2_SUP,

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

From All of Us Research Program, National Institutes of Health, SCV004845086.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (7)

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, ovarian, pancreatic, or prostate cancer (PMID: 16683254, 24156927, 26219728, 29446198, 32918181) and in an unaffected individual (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_001395). 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

ClinVar

Relating variation to medicine