• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
BRCA1 (HGNC:1100) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
BRCA1 DNA repair associated
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
RNF53, BRCC1, PPP1R53, FANCS
%HI
1.2(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0(Read more about gnomAD pLI score)
LOEUF
0.92(Read more about gnomAD LOEUF score)
Cytoband
17q21.31
Genomic Coordinates
GRCh37/hg19: chr17:41196312-41277381 NCBI Ensembl UCSC
GRCh38/hg38: chr17:43044295-43170327 NCBI Ensembl UCSC
MANE Select Transcript
NM_007294.4 ENST00000357654.9 (Read more about MANE Select)
Function
E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (PubMed:12890688, PubMed:14976165, PubMed:16818604, PubMed:17525340, PubMed:12887909, PubMed:10500182, PubMed:19261748). It is unclear whether it also mediates the formation of other types of polyubiquitin chains (PubMed:12890688). The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular path... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-20827
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
09/23/2021

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • breast-ovarian cancer, familial, susceptibility to, 1 Monarch
HI Evidence:
  • PUBMED: 32375709
    Van der Merwe et al. (2020) used MLPA and NGS to evaluate 744 patients with breast cancer or ovarian cancer in a South African cohort. 7 individuals were found to have large genomic rearrangements of BRCA1 (1.1% of total patients).
  • PUBMED: 21989022
    Garcia Casado et al. (2011) reported a de novo complete BRCA1 gene deletion in a Spanish woman. This patient has no apparent family history but developed bilateral metachronous breast cancer at the age of 28 and 37. MLPA profile suggests a deletion involving the entire BRCA1 gene. Array CGH confirmed that the deletion includes RND2, BRCA1,ΨBRCA1 and NBR2 genes. Non-paternity was excluded. Analysis of polymorphic markers within the BRCA1 gene indicates a maternal germ line origin of the deletion.
  • PUBMED: 11802209
    Mutation analysis for BRCA1 and BRCA2 gene were carried out in a comprehensive study of 989 patients with breast or ovarian cancer by German Consortium for Hereditary Breast and Ovarian Cancer. 77 mutations were found in BRCA1 gene. 65 of these mutations are nonsense or frameshift mutations causing truncated protein. The c.5266dupC (p.Gln1756Profs*74) (rs80357906) is the most common allele.
  • PUBMED: 24312913
    In a comprehensive review focusing on the global mutation spectrum of BRCA1 and BRCA2, loss of function mutations (Indels and splicing) account for a significant portion of reported mutations in BRCA1 across the globe (Northern Europe, Southern, Central and Western Europe, South America, Northern and Eastern Asia and Africa).
HI Evidence Comments:
Loss of function mutations in BRCA1 (nonsense, frameshift, splice site, and exonic deletions) as well as whole gene deletions of BRCA1 have been associated with cancer development (Genereviews and PMIDs: 21989022, 17661172, and 32375709). The penetrance associated with BRCA1 mutations is still an active area of study; however, patients with pathogenic BRCA1 mutations are thought to have an increased lifetime risk of developing breast cancer (46-87% in females, 1-2% in males), ovarian cancer (36-63%), prostate cancer (8.6% by age 65), and pancreatic cancer (1-3%) (Genereviews Table 2). An increased endometrial cancer risk has also been demonstrated (PMID:33710348).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
At this time there is no evidence to support the triplosensitivity of this gene. While several cases of BRCA1 duplication were reported (PMIDs:34146199, 32971473), these variants are believed to result in a loss-of-function.

Genomic View

Select assembly: (NC_000017.10) (NC_000017.11)