RAD51D |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- RAD51D (HGNC:9823) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- RAD51 paralog D
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- RAD51L3
- Alias symbols
- R51H3, Trad, HsTRAD
- %HI
- 59.17(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0(Read more about gnomAD pLI score)
- LOEUF
- 1.22(Read more about gnomAD LOEUF score)
- Cytoband
- 17q12
- Genomic Coordinates
-
GRCh37/hg19: chr17:33419240-33446879 NCBI Ensembl UCSC GRCh38/hg38: chr17:35092221-35119860 NCBI Ensembl UCSC - MANE Select Transcript
- NM_002878.4 ENST00000345365.11 (Read more about MANE Select)
- Function
- Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. Bind to single-stranded DNA (ssDNA) and has DNA-dependent ATPase activity. Part of the RAD51 paralog protein complex BCDX2 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 acts downstream of BRCA2 recruitment and upstream of RAD51 recruitment. BCDX2 binds predominantly to the intersection of the four duplex arms of... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-31761
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency
(3)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
01/09/2024
Haploinsufficiency (HI) Score Details
HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency
(Disclaimer)
HI Disease:
- familial ovarian cancer susceptibility, with or without breast cancer Monarch
HI Evidence:
-
PUBMED:
32359370
Suszynska et al. (2020) performed a meta-analysis of over 29,000 ovarian cancer (OC) patients plus 116,000 controls from gnomAD. 94 RAD51D variants were identified, the majority of which were either frameshift or nonsense sequence variants, 39 of which were distinct. While not included in formal calculation (since most included studies did not assess for larger rearrangements), ~16% of all variants in RAD51D involved exonic or multi-exonic deletions.
-
PUBMED:
34923718
Boni et al. (2022) performed a 10 year retrospective study since RAD51D had been added as a gene of significance for increased OC risk. They cite prior studies supporting RAD51D's role in increased OC risk, noting prior limitations that the evidence of pathogenicity in cancer predisposition was truncating mutations at that time (Gutierrez‐Enriquez et al., 2014; Osher et al., 2012; Wickramanayake et al., 2012). Boni et al. included both published data as well as unique cases from 95 probands from clinical studies (and their families). Boni's data accumulated a total of 73 nonsense variants, and 13 larger exonic/multiexonic CNVs (combination from both literature and unique clinical studies data). Other variants were seen including missense, frameshift, splice site, and start site loss variants. However, truncation/haploinsufficiency is considered the primary mechanism leading to predisposition.
HI Evidence Comments:
Germline truncating sequence variants and deletions in RAD51D have been identified in women affected by familial ovarian cancer, with or without breast cancer. Prior precedent studies concluded that RAD51D is a moderate penetrance susceptibility gene for ovarian cancer, with haploinsufficiency of the gene as the primary mechanism.
Data from these studies also describe personal history of breast cancer diagnosis, or family history of breast cancer, however additional studies are needed to confirm true risk increase specifically for breast cancer. For example, Yang et al. (2020) (PMID: 32107557) discuss the increased incidence of ER-/PR- breast cancer incidence in patients with RAD51D pathogenic variants, in addition to increased ovarian cancer risk. All unique variants noted in Rad51D were frameshift (14), nonsense (10) or splice site variants (5). The primary purpose of the study was to elucidate the age specific risks for carrier of pathogenic variants of RAD51C and RAD51D. Though this is the largest study of its kind to date, each age group reviewed did have a small overall study population.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
At this time, there is no evidence for triplosensitivity of RAD51D.
Genomic View
Select assembly:
(NC_000017.10)
(NC_000017.11)