ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000017.10) (NC_000017.11)
  • Haploinsufficiency score: 3
  • Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
29368626 Weber-Lassale et al. 2018 - study of 6341 patients with breast cancer and 706 patients with ovarian cancer, with 2189 matched female controls. Found LoF mutations (including nonsense mutations, splicing mutations, small intragenic deletions) in BRIP1 confer an increased risk for ovarian cancer, but not breast cancer. Specifically 18 truncating mutations were found in the ovarian cancer group (carrier frequency of 2.55%, and a higher carrier frequency in familial ovarian cancer cases) versus 3 LoF mutations found in the controls.
26720728 Norquist et al. 2016 - study of 1915 women with ovarian cancer, 26 mutations seen in BRIP1, including a nonsense mutation and intragenic deletions and insertions. After BRCA1/2, mutations in BRIP1 were the most common in the population of patients with ovarian cancer.
26315354 Ramus et al. 2015 - study of 3236 patients with ovarian cancer and 3431 controls, statistically significant difference seen in the number of deleterious mutations in BRIP1 between patients and controls. BRIP1 mutations (including nonsense mutations, splicing, intragenic deletions and insertions) found in 30 patients with ovarian cancer and 3 found in the control group.

Haploinsufficiency phenotype comments:

LOF mutations cause an increased risk cancer, specifically ovarian cancer. Previously thought to convey an increased risk for breast cancer, but newest literature (Weber-Lassalle 2018 (PMID 29368626), Couch 2017 (PMID 28418444), Easton 2016 (PMID 26921362), Tung 2016 (PMID 27296296) suggest no significant increased risk for breast, just the increased risk for ovarian cancer. Biallelic mutations in BRIP1 cause Fanconi anemia.

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

Triplosensitivity phenotype comment:

At this time there is no evidence to support the triplosensitivity of this gene