NM_000059.4(BRCA2):c.7762del (p.Ile2588fs) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Pathogenic (3 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:: RCV000113814.13

Allele description [Variation Report for NM_000059.4(BRCA2):c.7762del (p.Ile2588fs)]

NM_000059.4(BRCA2):c.7762del (p.Ile2588fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.7762del (p.Ile2588fs)

Other names:

7990del3ins2; 7990delA

HGVS:

NC_000013.11:g.32357886del
NG_012772.3:g.47407del
NM_000059.4:c.7762delMANE SELECT
NM_000059.4:c.7762delA
NP_000050.3:p.Ile2588fs
LRG_293:g.47407del
NC_000013.10:g.32932023del
NC_000013.10:g.32932023delA
NC_000013.11:g.32357886delA
NM_000059.3:c.7762delA
U43746.1:n.7990delA

Protein change:

I2588fs

Links:

Breast Cancer Information Core (BIC) (BRCA2): 7990&base_change=del A; dbSNP: rs80359679

NCBI 1000 Genomes Browser:

rs80359679

Molecular consequence:

NM_000059.4:c.7762del - 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
SCV000147176	Breast Cancer Information Core (BIC) (BRCA2)	no assertion criteria provided	Pathogenic (Jun 12, 2000)	germline	clinical testing
SCV000301202	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,
SCV002556628	Genetics and Molecular Pathology, SA Pathology See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 11, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9667259, 24504028, 29337092, 30267214, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000147176

Breast Cancer Information Core (BIC) (BRCA2)

no assertion criteria provided

Pathogenic
(Jun 12, 2000)

germline

clinical testing

SCV000301202

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,

SCV002556628

Genetics and Molecular Pathology, SA Pathology

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 11, 2022)

germline

clinical testing

PubMed (5)
[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	not provided	not provided	not provided	not provided	not provided	curation
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk.

Frank TS, Manley SA, Olopade OI, Cummings S, Garber JE, Bernhardt B, Antman K, Russo D, Wood ME, Mullineau L, Isaacs C, Peshkin B, Buys S, Venne V, Rowley PT, Loader S, Offit K, Robson M, Hampel H, Brener D, Winer EP, Clark S, et al.

J Clin Oncol. 1998 Jul;16(7):2417-25.

PubMed [citation]

PMID:: 9667259

Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status.

Cunningham JM, Cicek MS, Larson NB, Davila J, Wang C, Larson MC, Song H, Dicks EM, Harrington P, Wick M, Winterhoff BJ, Hamidi H, Konecny GE, Chien J, Bibikova M, Fan JB, Kalli KR, Lindor NM, Fridley BL, Pharoah PP, Goode EL.

Sci Rep. 2014 Feb 7;4:4026. doi: 10.1038/srep04026.

PubMed [citation]

PMID:: 24504028
PMCID:: PMC4168524

See all PubMed Citations (5)

Details of each submission

From Breast Cancer Information Core (BIC) (BRCA2), SCV000147176.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided
2	not provided	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), SCV000301202.2

#	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 Genetics and Molecular Pathology, SA Pathology, SCV002556628.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The BRCA2 c.7762del variant is classified as Pathogenic (PVS1, PS4_Moderate, PM2) This BRCA2 c.7762del variant is located in exon 16/27 and is predicted to cause a shift in the reading frame at codon 2588. BRCA2:c. 7762del (also described as BRCA1 4184del4 using legacy nomenclature) has been reported in multiple unrelated individuals and families with breast, ovarian and colon cancer (Cunningham et al., 2015 PMID: 24504028; Rosenthal et al, 2018 PMID: 30267214; Copson et al, 2018 PMID: 29337092). (Ps4_moderate) The variant has been reported in dbSNP (rs80359679) and has been reported as Pathogenic by other diagnostic laboratories (ClinVar Variation ID: 52405). It has not been reported in HGMD. literature: Frank (1998) J Clin Oncol, Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. PubMed: 9667259

#	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		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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