BRCA2

Gene Facts

• HGNC Symbol: BRCA2 (HGNC:1101)
• HGNC Name: BRCA2 DNA repair associated
• Gene type: protein-coding gene
• Locus type: gene with protein product
• Previous symbols: FANCD1, FACD, FANCD
• Alias symbols: FAD, FAD1, BRCC2, XRCC11
• %HI: 13.3
• pLI: 0
• LOEUF: 0.8
• Cytoband: 13q13.1
• Genomic Coordinates:

  GRCh37/hg19:	chr13:32889645-32974405
  GRCh38/hg38:	chr13:32315508-32400268

• MANE Select Transcript: NM_000059.4 ENST00000380152.8
• Function: Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51- ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

• Dosage ID: ISCA-33268
• ClinGen Curation ID: CCID:006761
• Curation Status: Complete
• Issue Type: Dosage Curation - Gene
• Haploinsufficiency: Sufficient Evidence for Haploinsufficiency (3)
• Triplosensitivity: No Evidence for Triplosensitivity (0)
• Last Evaluated: 07/14/2021

Haploinsufficiency (HI) Score Details

• HI Score: 3
• HI Evidence Strength: Sufficient Evidence for Haploinsufficiency

HI Disease

• Breast-ovarian cancer

HI Evidence

• PUBMED: 16199546
  Agata et al. (2005) analyzed 121 highly selected breast cancer families using BRCA2 MLPA and identified three large exonic germline deletions in BRCA2 (case1: deletion of exons 8-11, case 2: deletion of exons 17-18; case 3: deletion of exon 20).
• PUBMED: 17063271
  Gutiérrez-Enríquez et al. (2006) tried to estimate the prevalence of large genomic rearrangements in the BRCA2 gene in Spanish breast/ovarian cancer families. MLPA was employed to search gross deletions or duplications of BRCA2 in 335 Spanish moderate to high-risk breast/ovarian cancer families previously screened negative for point mutations by conventional methods. Three novel exonic deletions were identified by MLPA ( deletions of exon 2, exons 10-12 and exons 15-16).
• PUBMED: 25632310
  Timoteo et al. (2015) identified a large exonic deletion including BRCA2 exon 14, and this deletion is out of frame in a 64-year-old male patient with breast cancer.
• PUBMED: 12097290
  Murphy et al. (2002) sequenced the BRCA2 gene in 29 kindreds with pancreatic cancer and found that 5 patients (17.2%) had mutations that had previously been reported to be deleterious. Three patients harbored the common 6174delT frameshift mutation, and 2 had splice site mutations. A family history of breast cancer was reported in 2 of the 5 BRCA2 mutation carriers.
• PUBMED: 11897832
  Hamann et al. (2002) Sixty-eight probands from 68 breast/ovarian cancer families were studied for germline mutations of the BRCA2 gene. four frameshift variants (c.3036del4, c.3279delC, c.7296delTC, c.9894delT) and three nonsense variants (p.E1518X, p.Y1894X, p.K2013X) were identified in seven patients.
• PUBMED: 12569143
  Hahn et al (2003) identified three families carried germline frameshift mutations (c.6672insT, c.6819delTG, c.4075delGT) in the BRCA2 gene in 26 European families in which at least two first-degree relatives had a histologically confirmed diagnosis of pancreatic ductal adenocarcinoma.

• HI Evidence Comments: Many loss of function mutations have been described; see OMIM gene entry for details. Heterozygous mutations of BRCA2 cause susceptibility to breast and ovarian cancer (see OMIM), a phenotype that is not appropriate for our purposes. Homozygous mutations of BRCA2 cause Fanconi anemia (see GeneReviews), which is an appropriate phenotype but is an inappropriate mutational mechanism. BRCA2 large genomic rearrangement constitute <6% of all BRCA2 mutations, ≤0.5% of the total BRCA1/2 mutations.

Triplosensitivity (TS) Score Details

• TS Score: 0
• TS Evidence Strength: No Evidence for Triplosensitivity