XRCC2

X-ray repair cross complementing 2, the group of FA complementation groups

Basic information

Region (hg38): 7:152644775-152676193

Links

ENSG00000196584 ∙ NCBI:7516 ∙ OMIM:600375 ∙ HGNC:12829 ∙ Uniprot:O43543 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Fanconi anemia (Supportive), mode of inheritance: AR
• male infertility with azoospermia or oligozoospermia due to single gene mutation (Supportive), mode of inheritance: AD
• breast cancer (Disputed Evidence), mode of inheritance: AD
• Fanconi anemia complementation group U (Moderate), mode of inheritance: AR
• spermatogenic failures 50 (Limited), mode of inheritance: Unknown
• Fanconi anemia complementation group U (Limited), mode of inheritance: AR
• premature ovarian failure 17 (Limited), mode of inheritance: Unknown
• familial ovarian cancer (No Known Disease Relationship), mode of inheritance: AD
• hereditary breast carcinoma (Refuted Evidence), mode of inheritance: AD
• Fanconi anemia complementation group U (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fanconi anemia, complementation group U	AR	Cardiovascular	Fanconi anemia can involve congenital cardiac (and other) anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic	22232082; 27208205; 30042186; 30489636
In individuals with Fanconi anemia, complementation group U, hematologic or oncologic manifestations have not been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the XRCC2 gene.

• Hereditary cancer-predisposing syndrome (429 variants)
• not provided (315 variants)
• not specified (71 variants)
• Fanconi anemia complementation group U (23 variants)
• XRCC2-related condition (5 variants)
• Inborn genetic diseases (2 variants)
• Hereditary breast ovarian cancer syndrome (2 variants)
• Colorectal cancer (1 variants)
• Spermatogenic failures 50 (1 variants)
• Fanconi anemia complementation group U;Spermatogenic failures 50;Premature ovarian failure 17 (1 variants)
• Breast carcinoma (1 variants)
• Colon cancer (1 variants)
• Premature ovarian failure 17 (1 variants)
• Short stature, microcephaly, and endocrine dysfunction (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the XRCC2 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			3	116		119
missense			310	6	1	317
nonsense		2	11			13
start loss		1	1			2
frameshift	1	7	18			26
inframe indel			10			10
splice donor/acceptor (+/-2bp)		2	2			4
splice region			2	6		8
non coding			4	29	13	46
Total	1	12	359	151	14

Highest pathogenic variant AF is 0.00000656

Variants in XRCC2

This is a list of pathogenic ClinVar variants found in the XRCC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-152646717-T-G		not specified	Uncertain significance (Apr 03, 2015)
7-152648413-GA-G			Benign (Aug 07, 2019)
7-152648413-GAA-G			Benign (Aug 07, 2019)
7-152648459-G-A			Benign (Jun 23, 2018)
7-152648602-C-G			Benign (Mar 03, 2015)
7-152648641-A-G		Hereditary cancer-predisposing syndrome • not specified	Benign (Apr 02, 2021)
7-152648641-ATCAACAAAAT-A		Hereditary cancer-predisposing syndrome	Uncertain significance (Jun 12, 2023)
7-152648643-C-T		not specified • Hereditary cancer-predisposing syndrome	Conflicting classifications of pathogenicity (Nov 05, 2022)
7-152648645-A-G		Hereditary cancer-predisposing syndrome	Likely benign (Jan 10, 2022)
7-152648646-C-T		Hereditary cancer-predisposing syndrome	Uncertain significance (Sep 15, 2020)
7-152648651-T-C		Hereditary cancer-predisposing syndrome	Likely benign (Oct 27, 2022)
7-152648652-T-C		Hereditary cancer-predisposing syndrome	Uncertain significance (Jul 14, 2021)
7-152648653-C-T		Hereditary cancer-predisposing syndrome	Uncertain significance (Jul 04, 2021)
7-152648656-C-A			Uncertain significance (Jul 14, 2022)
7-152648656-C-T		Hereditary cancer-predisposing syndrome	Uncertain significance (Jun 21, 2021)
7-152648657-C-G		Hereditary cancer-predisposing syndrome	Likely benign (Oct 12, 2022)
7-152648657-C-T		not specified • Hereditary cancer-predisposing syndrome	Conflicting classifications of pathogenicity (Feb 18, 2023)
7-152648658-C-T		Hereditary cancer-predisposing syndrome	Uncertain significance (Jul 30, 2023)
7-152648659-C-T		Hereditary cancer-predisposing syndrome	Uncertain significance (Nov 15, 2023)
7-152648660-A-C		Hereditary cancer-predisposing syndrome	Uncertain significance (Sep 13, 2023)
7-152648660-A-G		Hereditary cancer-predisposing syndrome • XRCC2-related disorder	Benign/Likely benign (Dec 06, 2023)
7-152648663-T-G		Hereditary cancer-predisposing syndrome	Uncertain significance (Jun 10, 2021)
7-152648662-T-TGGCTGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCATGAGGTCAGGAGATCNNNNNNNNNNNNAAAAAAAAAAAAAAAAA			Uncertain significance (Mar 10, 2018)
7-152648664-T-C		Hereditary cancer-predisposing syndrome	Uncertain significance (Jun 25, 2023)
7-152648664-T-G		Hereditary cancer-predisposing syndrome	Uncertain significance (Jun 10, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
XRCC2	protein_coding	protein_coding	ENST00000359321	3	31387

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.96e-7	0.373	125665	0	82	125747	0.000326

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.127	152	148	1.03	0.00000740	1836
Missense in Polyphen		58	57.447	1.0096		731
Synonymous	1.09	43	53.1	0.810	0.00000250	534
Loss of Function	0.578	11	13.3	0.829	9.10e-7	141

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000560	0.000558
Ashkenazi Jewish	0.000402	0.000397
East Asian	0.0000558	0.0000544
Finnish	0.000241	0.000231
European (Non-Finnish)	0.000433	0.000431
Middle Eastern	0.0000558	0.0000544
South Asian	0.000198	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA, thought to repair chromosomal fragmentation, translocations and deletions. Part of the Rad21 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 the Holliday junction 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. {ECO:0000269|PubMed:11751635, ECO:0000269|PubMed:11834724, ECO:0000269|PubMed:21276791, ECO:0000269|PubMed:23149936, ECO:0000269|PubMed:27233470}.
• Disease: DISEASE: Fanconi anemia, complementation group U (FANCU) [MIM:617247]: 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:22232082}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: 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;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: 0.223

Intolerance Scores

• loftool: 0.862
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.22

Haploinsufficiency Scores

• pHI: 0.247
• hipred: N
• hipred_score: 0.251
• ghis: 0.417

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.684

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Xrcc2
• Phenotype: neoplasm; 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); respiratory system phenotype; embryo 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); limbs/digits/tail phenotype; growth/size/body region 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); homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype

Gene ontology

• Biological process: mitotic cell cycle;double-strand break repair via homologous recombination;in utero embryonic development;somitogenesis;DNA repair;centrosome cycle;response to X-ray;response to gamma radiation;multicellular organism growth;strand invasion;negative regulation of neuron apoptotic process;positive regulation of neurogenesis;meiotic cell cycle;regulation of fibroblast apoptotic process
• Cellular component: nucleoplasm;replication fork;cytoplasm;centrosome;Rad51B-Rad51C-Rad51D-XRCC2 complex;intracellular membrane-bounded organelle
• Molecular function: four-way junction DNA binding;protein binding;ATP binding;DNA-dependent ATPase activity