ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function 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.

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.