BRCA2
BRCA2 DNA repair associated, the group of FA complementation groups
Basic information
Region (hg38): 13:32315086-32400268
Previous symbols: [ "FANCD1", "FACD", "FANCD" ]
Links
Phenotypes
GenCC
Source:
- sarcoma (Moderate), mode of inheritance: AD
- breast-ovarian cancer, familial, susceptibility to, 2 (Strong), mode of inheritance: AD
- pancreatic cancer, susceptibility to, 2 (Strong), mode of inheritance: AD
- breast-ovarian cancer, familial, susceptibility to, 2 (Definitive), mode of inheritance: AD
- Fanconi anemia complementation group D1 (Definitive), mode of inheritance: AR
- Fanconi anemia (Supportive), mode of inheritance: AR
- hereditary breast ovarian cancer syndrome (Supportive), mode of inheritance: AD
- familial prostate carcinoma (Definitive), mode of inheritance: AD
- Fanconi anemia complementation group D1 (Definitive), mode of inheritance: AR
- Fanconi anemia complementation group D1 (Strong), mode of inheritance: AR
- breast-ovarian cancer, familial, susceptibility to, 2 (Strong), mode of inheritance: AD
- breast-ovarian cancer, familial, susceptibility to, 2 (Definitive), mode of inheritance: AD
- Fanconi anemia complementation group D1 (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Breast-ovarian cancer, familial, susceptibility to; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3; Fanconi anemia, complementation group D1; Wilms tumor; Medulloblastoma | AD/AR | Allergy/Immunology/Infectious; Cardiovascular; Hematologic; Oncologic | For hereditary breast and ovarian cancer, though the availability of empirical data is incomplete as applies to both screening strategies and prophylactic treatment, surveillance is based on the age of affected family members (for breast cancer, surveillance includes self-examination as well as regular clinical examinations, mammography, and MRI; for ovarian cancer, screening includes regular pelvic examination, transvaginal ultrasounds with Doppler, and CA-125 measurement; for prostate cancer, screening includes regular rectal examination and PSA measurement); Prophylactic mastectomy and/or oophorectomy, as well as chemoprevention (eg, with tamoxifen) are described; Treatment of breast and ovarian cancer follows standard guidelines (ie, that apply more generally), though, new targeted therapies are under investigation; There are little empiric data regarding other cancer types, though awareness may allow early diagnosis and treatment; For individuals with metastatic Prostate cancer, management with PARP-inhibitors has been described as improving progression-free survival; For Fanconi anemia: specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count), and 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; Craniofacial; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Oncologic | 8091231; 8524414; 7597059; 9140390; 10441598; 10807385; 12036267; 11133358; 12065746; 12097290; 12161607; 12023992; 12023993; 14569130; 12556369; 14670928; 15912495; 15948173; 15689453; 16825431; 18264087; 18349832; 18355772; 18413374; 19190154; 21118973; 21593217; 21531449; 20216074; 22614657; 23285130; 31157963 |
| Variants may also predispose to a number of other malignancies |
ClinVar
This is a list of variants' phenotypes submitted to
- Breast-ovarian cancer, familial, susceptibility to, 2 (2938 variants)
- Hereditary breast ovarian cancer syndrome (2403 variants)
- Hereditary cancer-predisposing syndrome (2015 variants)
- not provided (1046 variants)
- Familial cancer of breast (757 variants)
- Breast and/or ovarian cancer (129 variants)
- Malignant tumor of breast (113 variants)
- Breast-ovarian cancer, familial, susceptibility to, 1 (79 variants)
- BRCA2-related disorder (65 variants)
- Gastric cancer (63 variants)
- 8 conditions (62 variants)
- Breast neoplasm (50 variants)
- not specified (34 variants)
- Breast carcinoma (27 variants)
- Fanconi anemia complementation group D1 (25 variants)
- Neoplasm of ovary (24 variants)
- Malignant tumor of urinary bladder (16 variants)
- Fanconi anemia complementation group D1;Hereditary breast ovarian cancer syndrome (11 variants)
- Malignant tumor of prostate (8 variants)
- Carcinoma of pancreas (7 variants)
- BRCA2-related cancer predisposition (7 variants)
- Rhabdomyosarcoma (6 variants)
- 9 conditions (6 variants)
- Breast-ovarian cancer, familial, susceptibility to, 2;Hereditary breast ovarian cancer syndrome (5 variants)
- Endometrial carcinoma (4 variants)
- Pancreatic cancer, susceptibility to, 2 (4 variants)
- Fanconi anemia (3 variants)
- Uterine corpus cancer (3 variants)
- Wilms tumor 1 (3 variants)
- Medulloblastoma (3 variants)
- Cancer of the pancreas (3 variants)
- Glioma susceptibility 3 (2 variants)
- Inherited ovarian cancer (without breast cancer) (2 variants)
- Ovarian cancer (2 variants)
- Hereditary breast ovarian cancer syndrome;Fanconi anemia complementation group D1 (2 variants)
- Infiltrating duct carcinoma of breast (2 variants)
- Genetic non-acquired premature ovarian failure (2 variants)
- Hereditary breast ovarian cancer syndrome;Breast-ovarian cancer, familial, susceptibility to, 2 (1 variants)
- See cases (1 variants)
- Intellectual disability (1 variants)
- Breast-ovarian cancer, familial, susceptibility to, 2;Fanconi anemia complementation group D1 (1 variants)
- NICE approved PARP inhibitor treatment (1 variants)
- Diffuse midline glioma, H3 K27-altered (1 variants)
- Carcinoma of colon (1 variants)
- bilateral breast cancer (1 variants)
- Polyposis syndrome, hereditary mixed, 1 (1 variants)
- Focal-onset seizure (1 variants)
- FLG-related disorder (1 variants)
- Familial cancer of breast;Breast-ovarian cancer, familial, susceptibility to, 2;Malignant tumor of prostate (1 variants)
- Ovarian cancer;Malignant tumor of breast (1 variants)
- BAP1-related tumor predisposition syndrome (1 variants)
- Malignant lymphoma, large B-cell, diffuse (1 variants)
- Colorectal cancer (1 variants)
- Breast cancer, susceptibility to (1 variants)
- Neuroendocrine tumor of pancreas (1 variants)
- Chordoma (1 variants)
- Polydactyly (1 variants)
- Familial cancer of breast;Breast-ovarian cancer, familial, susceptibility to, 2 (1 variants)
- Metastatic Prostate Small Cell Carcinoma;Malignant tumor of prostate (1 variants)
- Diffuse intrinsic pontine glioma (1 variants)
- Ateleiotic dwarfism (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the BRCA2 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 | 33 | 2671 | 44 | 2748 | ||
| missense | 24 | 59 | 3124 | 203 | 135 | 3545 |
| nonsense | 965 | 84 | 1066 | |||
| start loss | 16 | |||||
| frameshift | 3105 | 256 | 19 | 20 | 3400 | |
| inframe indel | 233 | 245 | ||||
| splice donor/acceptor (+/-2bp) | 108 | 115 | 14 | 238 | ||
| splice region | 13 | 20 | 176 | 142 | 7 | 358 |
| non coding | 14 | 133 | 636 | 530 | 1319 | |
| Total | 4226 | 527 | 3570 | 3542 | 712 |
Highest pathogenic variant AF is 0.000171
Variants in BRCA2
This is a list of pathogenic ClinVar variants found in the BRCA2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| BRCA2 | protein_coding | protein_coding | ENST00000544455 | 26 | 84195 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 2.36e-25 | 1.00 | 125654 | 0 | 94 | 125748 | 0.000374 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -1.29 | 1812 | 1.66e+3 | 1.09 | 0.0000806 | 22668 |
| Missense in Polyphen | 410 | 405.32 | 1.0116 | 6007 | ||
| Synonymous | 0.214 | 587 | 594 | 0.989 | 0.0000302 | 6253 |
| Loss of Function | 4.92 | 61 | 119 | 0.513 | 0.00000539 | 1807 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00106 | 0.00106 |
| Ashkenazi Jewish | 0.0000994 | 0.0000992 |
| East Asian | 0.000217 | 0.000217 |
| Finnish | 0.000554 | 0.000554 |
| European (Non-Finnish) | 0.000291 | 0.000290 |
| Middle Eastern | 0.000217 | 0.000217 |
| South Asian | 0.000294 | 0.000294 |
| Other | 0.000654 | 0.000652 |
dbNSFP
Source:
- Function
- FUNCTION: Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop- associated DNA damage and thus transcription-associated genomic instability. Silencing of BRCA2 promotes R-loop accumulation at actively transcribed genes in replicating and non-replicating cells, suggesting that BRCA2 mediates the control of R-loop associated genomic instability, independently of its known role in homologous recombination (PubMed:24896180). {ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15199141, ECO:0000269|PubMed:15671039, ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:20729832, ECO:0000269|PubMed:20729858, ECO:0000269|PubMed:20729859, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:21719596, ECO:0000269|PubMed:24485656, ECO:0000269|PubMed:24896180}.;
- Disease
- DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:10399947, ECO:0000269|PubMed:10978364, ECO:0000269|PubMed:11139248, ECO:0000269|PubMed:11241844, ECO:0000269|PubMed:11948477, ECO:0000269|PubMed:12145750, ECO:0000269|PubMed:12373604, ECO:0000269|PubMed:12442274, ECO:0000269|PubMed:12442275, ECO:0000269|PubMed:12938098, ECO:0000269|PubMed:14722926, ECO:0000269|PubMed:15026808, ECO:0000269|PubMed:15172753, ECO:0000269|PubMed:15365993, ECO:0000269|PubMed:16793542, ECO:0000269|PubMed:24013206, ECO:0000269|PubMed:8640237, ECO:0000269|PubMed:9150152, ECO:0000269|PubMed:9609997, ECO:0000269|PubMed:9654203, ECO:0000269|PubMed:9971877}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Pancreatic cancer 2 (PNCA2) [MIM:613347]: A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue. {ECO:0000269|PubMed:9140390}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Breast-ovarian cancer, familial, 2 (BROVCA2) [MIM:612555]: 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. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Fanconi anemia complementation group D1 (FANCD1) [MIM:605724]: 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:12065746, ECO:0000269|PubMed:14670928, ECO:0000269|PubMed:16825431, ECO:0000269|PubMed:21719596}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Glioma 3 (GLM3) [MIM:613029]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. {ECO:0000269|PubMed:15689453}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Fanconi anemia pathway - Homo sapiens (human);Breast cancer - Homo sapiens (human);Homologous recombination - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Integrated Breast Cancer Pathway;Homologous recombination;Signaling Pathways in Glioblastoma;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;DNA Double-Strand Break Repair;role of brca1 brca2 and atr in cancer susceptibility;Homology Directed Repair;p73 transcription factor network;Fanconi anemia pathway;Validated transcriptional targets of deltaNp63 isoforms;FOXM1 transcription factor network;ATR signaling pathway;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
- 0.703
Intolerance Scores
- loftool
- 0.0896
- rvis_EVS
- 3.73
- rvis_percentile_EVS
- 99.59
Haploinsufficiency Scores
- pHI
- 0.971
- hipred
- Y
- hipred_score
- 0.598
- ghis
- 0.415
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.854
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Brca2
- Phenotype
- limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; immune system phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal 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); reproductive system phenotype; hematopoietic system phenotype; neoplasm; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- brca2
- Affected structure
- spermatocyte
- Phenotype tag
- abnormal
- Phenotype quality
- apoptotic
Gene ontology
- Biological process
- mitotic cytokinesis;telomere maintenance via recombination;double-strand break repair via homologous recombination;oocyte maturation;inner cell mass cell proliferation;nucleotide-excision repair;double-strand break repair;DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator;male meiosis I;brain development;cell aging;response to X-ray;response to UV-C;response to gamma radiation;hemopoiesis;regulation of cytokinesis;negative regulation of mammary gland epithelial cell proliferation;intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator;histone H3 acetylation;histone H4 acetylation;positive regulation of transcription, DNA-templated;positive regulation of mitotic cell cycle;replication fork protection;centrosome duplication;establishment of protein localization to telomere;mitotic recombination-dependent replication fork processing
- Cellular component
- nuclear chromosome, telomeric region;lateral element;nucleus;nucleoplasm;centrosome;cytosol;secretory granule;protein-containing complex;BRCA2-MAGE-D1 complex
- Molecular function
- protease binding;single-stranded DNA binding;histone acetyltransferase activity;protein binding;protein C-terminus binding;H3 histone acetyltransferase activity;H4 histone acetyltransferase activity;identical protein binding;gamma-tubulin binding