NM_000059.4(BRCA2):c.7762del (p.Ile2588fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 18, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000509870.12

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]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000608142	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Apr 18, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24504028, 24728189, 9667259 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000608142

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Apr 18, 2018)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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	clinical testing

Citations

PubMed

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

The contribution of deleterious germline mutations in BRCA1, BRCA2 and the mismatch repair genes to ovarian cancer in the population.

Song H, Cicek MS, Dicks E, Harrington P, Ramus SJ, Cunningham JM, Fridley BL, Tyrer JP, Alsop J, Jimenez-Linan M, Gayther SA, Goode EL, Pharoah PD.

Hum Mol Genet. 2014 Sep 1;23(17):4703-9. doi: 10.1093/hmg/ddu172. Epub 2014 Apr 12.

PubMed [citation]

PMID:: 24728189
PMCID:: PMC4119409

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000608142.5

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

Description

The c.7762delA pathogenic mutation, located in coding exon 15 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 7762, causing a translational frameshift with a predicted alternate stop codon (p.I2588Yfs*60). This pathogenic mutation has been reported in an early-onset breast cancer family and in a series of >900 epithelial ovarian cancer patients (Frank TS et al. J. Clin. Oncol. 1998 Jul;16:2417-25; Cunningham JM et al. Sci Rep. 2014 Feb;4:4026). In one case control study, this alteration was detected in 2/2222 individuals with high-grade serous epithelial ovarian cancer and 0/1528 matched controls. (Song H et al. Hum. Mol. Genet. 2014 Sep;23:4703-9). Of note, this mutation is also designated as 7990delA and I2588fs in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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

Last Updated: Nov 3, 2024

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