ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000013.10) (NC_000013.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
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).
17063271 Guti?rrez-Enr?quez 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).
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.
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.
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.

Haploinsufficiency phenotype 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 score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity