RAD51C

RAD51 paralog C, the group of FA complementation groups

Basic information

Region (hg38): 17:58692572-58735611

Links

ENSG00000108384 ∙ NCBI:5889 ∙ OMIM:602774 ∙ HGNC:9820 ∙ Uniprot:O43502 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Fanconi anemia complementation group O (Strong), mode of inheritance: AR
• breast-ovarian cancer, familial, susceptibility to, 3 (Strong), mode of inheritance: AD
• Fanconi anemia (Supportive), mode of inheritance: AR
• hereditary breast ovarian cancer syndrome (Supportive), mode of inheritance: AD
• Fanconi anemia complementation group O (Moderate), mode of inheritance: AR
• breast-ovarian cancer, familial, susceptibility to, 3 (Limited), mode of inheritance: AD
• breast-ovarian cancer, familial, susceptibility to, 3 (Definitive), mode of inheritance: AD
• Fanconi anemia complementation group O (Strong), mode of inheritance: AR
• breast-ovarian cancer, familial, susceptibility to, 3 (Strong), mode of inheritance: AD
• hereditary breast carcinoma (Disputed Evidence), mode of inheritance: AD
• Fanconi anemia complementation group O (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Breast-ovarian cancer, familial, susceptibility to; Fanconi anemia goup O	AD/AR	Allergy/Immunology/Infectious; Cardiovascular; Hematologic; Oncologic	In Breast-ovarian cancer susceptibility, surveillance (similar to that indicated in individuals with BRCA1 or BRCA2 variants) may allow early detection and treatment of tumors, which may reduce morbidity and mortality; For Fanconi anemia, specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; surveillance for complications such as bone marrow failure is recommended; Fanconi anemia can involve congenital cardiac (and other) anomalies, and awareness may allow early management	Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; Oncologic; Renal	20400964; 20400963; 21568838; 20301575

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RAD51C gene.

• Fanconi anemia complementation group O (1299 variants)
• Hereditary cancer-predisposing syndrome (1118 variants)
• not provided (327 variants)
• Breast-ovarian cancer, familial, susceptibility to, 3 (278 variants)
• not specified (208 variants)
• Breast-ovarian cancer, familial, susceptibility to, 3;Fanconi anemia complementation group O (72 variants)
• Hereditary breast ovarian cancer syndrome (58 variants)
• Breast and/or ovarian cancer (40 variants)
• Fanconi anemia complementation group O;Breast-ovarian cancer, familial, susceptibility to, 3 (30 variants)
• Malignant tumor of breast (20 variants)
• RAD51C-related condition (17 variants)
• Neoplasm of ovary (12 variants)
• Gastric cancer (8 variants)
• Ovarian cancer (6 variants)
• Fanconi anemia (4 variants)
• Inborn genetic diseases (4 variants)
• Breast and Ovarian Cancer Susceptibility (4 variants)
• Hereditary cancer (3 variants)
• Familial cancer of breast (3 variants)
• Breast carcinoma (3 variants)
• Endometrial carcinoma (2 variants)
• RAD51C-Related Disorders (2 variants)
• Carcinoma of colon (2 variants)
• Hereditary site-specific ovarian cancer syndrome (2 variants)
• Microcephaly (1 variants)
• Uterine corpus cancer (1 variants)
• Premature ovarian failure (1 variants)
• Breast-ovarian cancer, familial, susceptibility to, 1 (1 variants)
• Premature ovarian insufficiency (1 variants)
• Familial ovarian carcinoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAD51C gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	273	1	279
missense		7	843	2	1	853
nonsense	37	18	2			57
start loss	1		6			7
frameshift	80	36	7			123
inframe indel			15			15
splice donor/acceptor (+/-2bp)	3	39	6			48
splice region		8	44	35		87
non coding			31	166	9	206
Total	121	100	915	441	11

Highest pathogenic variant AF is 0.0000328

Variants in RAD51C

This is a list of pathogenic ClinVar variants found in the RAD51C region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-58692595-C-G		not specified	Likely benign (Nov 30, 2017)
17-58692596-G-T		not specified	Benign (Sep 14, 2015)
17-58692603-T-A		not specified	Likely benign (Mar 30, 2017)
17-58692603-T-C			Benign (Jul 23, 2015)
17-58692605-C-G		not specified	Likely benign (Dec 11, 2017)
17-58692608-A-G		not specified	Likely benign (Mar 04, 2016)
17-58692608-AG-A		not specified	Likely benign (Sep 19, 2016)
17-58692615-C-T		not specified	Likely benign (Sep 19, 2016)
17-58692616-T-G		not specified	Likely benign (Apr 01, 2016)
17-58692618-C-T		Breast and Ovarian Cancer Susceptibility • Fanconi anemia • not specified • RAD51C-related disorder	Benign/Likely benign (Sep 09, 2022)
17-58692620-C-A		not specified	Likely benign (Dec 18, 2017)
17-58692620-C-G		not specified	Likely benign (Jun 15, 2016)
17-58692620-C-T		not specified	Likely benign (Jul 28, 2017)
17-58692622-G-C		not specified	Likely benign (Jul 25, 2016)
17-58692624-G-A		Hereditary cancer-predisposing syndrome	Likely benign (Aug 11, 2015)
17-58692624-G-C		Hereditary cancer-predisposing syndrome	Uncertain significance (Jul 03, 2019)
17-58692624-G-T		Hereditary cancer-predisposing syndrome	Uncertain significance (Apr 24, 2019)
17-58692625-G-A		not specified • Hereditary cancer-predisposing syndrome	Conflicting classifications of pathogenicity (Aug 15, 2023)
17-58692625-G-T		Hereditary cancer-predisposing syndrome • not specified • Fanconi anemia complementation group O	Conflicting classifications of pathogenicity (Jan 22, 2021)
17-58692626-T-C		Hereditary cancer-predisposing syndrome	Likely benign (Dec 01, 2017)
17-58692626-T-G		Hereditary cancer-predisposing syndrome	Likely benign (Jul 06, 2017)
17-58692629-G-T		Hereditary cancer-predisposing syndrome	Likely benign (Mar 17, 2017)
17-58692629-GCAGGTGAGCCTGCGATGCGCGGGAAGA-G		Breast-ovarian cancer, familial, susceptibility to, 3	Pathogenic (May 03, 2021)
17-58692631-A-G		Hereditary cancer-predisposing syndrome	Benign/Likely benign (Jul 07, 2017)
17-58692632-G-C		Hereditary cancer-predisposing syndrome	Likely benign (Mar 16, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAD51C	protein_coding	protein_coding	ENST00000337432	9	41770

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.19e-14	0.0160	125632	0	116	125748	0.000461

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.126	200	205	0.975	0.0000104	2419
Missense in Polyphen		45	50.51	0.89092		533
Synonymous	0.184	69	71.0	0.972	0.00000310	750
Loss of Function	-0.110	20	19.5	1.03	0.00000106	230

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000426	0.000424
Ashkenazi Jewish	0.00	0.00
East Asian	0.000818	0.000816
Finnish	0.000416	0.000416
European (Non-Finnish)	0.000475	0.000475
Middle Eastern	0.000818	0.000816
South Asian	0.000817	0.000817
Other	0.000653	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential for the homologous recombination (HR) pathway of DNA repair. Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. Part of the RAD21 paralog protein complexes BCDX2 and CX3 which act at different stages of the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 seems to act downstream of BRCA2 recruitment and upstream of RAD51 recruitment; CX3 seems to act downstream of RAD51 recruitment; both complexes bind predominantly to the intersection of the four duplex arms of the Holliday junction (HJ) and to junction of replication forks. The BCDX2 complex was originally reported to bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA. The BCDX2 subcomplex RAD51B:RAD51C exhibits single-stranded DNA-dependent ATPase activity suggesting an involvement in early stages of the HR pathway. Involved in RAD51 foci formation in response to DNA damage suggesting an involvement in early stages of HR probably in the invasion step. Has an early function in DNA repair in facilitating phosphorylation of the checkpoint kinase CHEK2 and thereby transduction of the damage signal, leading to cell cycle arrest and HR activation. Participates in branch migration and HJ resolution and thus is important for processing HR intermediates late in the DNA repair process; the function may be linked to the CX3 complex. Part of a PALB2-scaffolded HR complex containing BRCA2 and which is thought to play a role in DNA repair by HR. Protects RAD51 from ubiquitin-mediated degradation that is enhanced following DNA damage. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51 and XRCC3. Contributes to DNA cross-link resistance, sister chromatid cohesion and genomic stability. Involved in maintaining centrosome number in mitosis. {ECO:0000269|PubMed:14716019, ECO:0000269|PubMed:16215984, ECO:0000269|PubMed:16395335, ECO:0000269|PubMed:19451272, ECO:0000269|PubMed:19783859, ECO:0000269|PubMed:20413593, ECO:0000269|PubMed:23108668, ECO:0000269|PubMed:23149936}.
• Disease: DISEASE: Fanconi anemia complementation group O (FANCO) [MIM:613390]: A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. {ECO:0000269|PubMed:20400963, ECO:0000269|PubMed:24141787}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Breast-ovarian cancer, familial, 3 (BROVCA3) [MIM:613399]: A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate. {ECO:0000269|PubMed:20400964, ECO:0000269|PubMed:21990120, ECO:0000269|PubMed:24141787}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fanconi anemia pathway - Homo sapiens (human);Homologous recombination - Homo sapiens (human);HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;DNA Double-Strand Break Repair;Homology Directed Repair;Factors involved in megakaryocyte development and platelet production;Hemostasis;Presynaptic phase of homologous DNA pairing and strand exchange;Homologous DNA Pairing and Strand Exchange;Resolution of D-loop Structures through Holliday Junction Intermediates;Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA);Resolution of D-Loop Structures;HDR through Homologous Recombination (HRR) (Consensus)

Recessive Scores

• pRec: 0.166

Intolerance Scores

• loftool: 0.704
• rvis_EVS: 0.11
• rvis_percentile_EVS: 61.73

Haploinsufficiency Scores

• pHI: 0.851
• hipred: Y
• hipred_score: 0.575
• ghis: 0.589

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.972

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Rad51c
• Phenotype: embryo phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: telomere maintenance via recombination;double-strand break repair via homologous recombination;DNA repair;DNA recombination;sister chromatid cohesion;female meiosis sister chromatid cohesion;reciprocal meiotic recombination;male meiosis I;spermatogenesis;blood coagulation;positive regulation of G2/M transition of mitotic cell cycle
• Cellular component: nucleus;nucleoplasm;replication fork;cytoplasm;mitochondrion;cytosol;cell junction;Rad51B-Rad51C-Rad51D-XRCC2 complex;Rad51C-XRCC3 complex;intracellular membrane-bounded organelle;perinuclear region of cytoplasm;Holliday junction resolvase complex
• Molecular function: four-way junction DNA binding;DNA binding;protein binding;ATP binding;DNA-dependent ATPase activity;crossover junction endodeoxyribonuclease activity