ClinGen Dosage Sensitivity Curation Page
RAD51C
- Curation Status: Complete
- id: ISCA-4342
- Date last evaluated: 2020-07-08
- Issue Type: ClinGen Gene Curation
- Gene type: protein-coding
- ClinGen: Search for information about RAD51C at clinicalgenome.org
- Entrez Gene: https://www.ncbi.nlm.nih.gov/gene/5889
- OMIM: https://omim.org/entry/613399
- Gene Reviews: https://www.ncbi.nlm.nih.gov/books/NBK1401/?term=RAD51C
- ClinGen Haploinsufficiency Score: 3
- ClinGen Triplosensitivity Score: 0
Select assembly:
(NC_000017.10)
(NC_000017.11)
- Haploinsufficiency score: 3
- Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
| 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