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
21990120 This study characterized the presence of disease-causing variants in the RAD51C gene among 1053 individuals with hereditary breast cancer, 335 with hereditary breast and ovarian cancer, and 267 unselected individuals with ovarian cancer, finding 3 truncating variants. The p.Val25CysFS*3 was detected in a family with 2 reports ovarian cancer; the p.Gln133X was reported in a family with 3 women diagnosed with both breast and ovarian cancer, one with bilateral breast cancer. Additionally the p.Gly77ValFs*24 was reported in an unselected patient with no available family history with ovarian cancer and a metachronous breast cancer.
24800917 Study of 348 BRCA1/2 negative individuals with either breast or ovarian cancer found at 3 different truncating variants (p.Cys68*, c.Tyr75*, and p.Ser234*) in 3 separate families segregating breast cancer, ovarian cancer as well as leukemia( for p.Cys68*).
20400964 Additional study of 1100 unrelated individuals from pedigrees with either breast or ovarian cancer or both. This study identified 3 different loss of function variants. The p.Cis176Leufs*26 in a family with one individual with ovarian cancer, one with breast cancer and non-Hodgkin lymphoma, and one individual with breast cancer. The canonical splice site variant c.145+1G>T resulting in an abnormal RNA message was found in a family with two individuals with breast cancer (BC) an one with ovarian cancer (OC). Finally, the c.904+5G>T also leading to an abnormal mRNA was found in a family with 2 individuals with BC and 2 with OC

Haploinsufficiency phenotype comments:

Biallelic missense variants have been reported in patients with Fanconi Anemia type O (FANCO) (PMID: 20400964, 20400963). Loss of function variants are associated with an increased risk for ovarian cancer and possibly breast cancer.

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

Triplosensitivity phenotype comment:

no evidence for triplosensitivity