XRCC2

Chr 7AR

X-ray repair cross complementing 2

Also known as: FANCU, POF17, SPGF50

NCBI Gene: 7516ENSG00000196584UniProt: O43543OMIM: 600375

This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. This gene is involved in the repair of DNA double-strand breaks by homologous recombination and it functionally complements Chinese hamster irs1, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents. [provided by RefSeq, Jul 2008]

GeneReviewsOMIMResearchGenerating clinical summary…
DNmechanismARLOEUF 1.373 OMIM phenotypes
Clinical Summary— XRCC2
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Gene-Disease Validity (ClinGen)
Fanconi anemia complementation group U · ARLimited

Limited evidence — not for standalone diagnostic reporting

3 total gene-disease associations curated

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 540 VUS of 856 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — XRCC2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
1.37LOEUF
pLI 0.000
Z-score 0.58
OE 0.83 (0.52–1.37)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.13Z-score
OE missense 1.03 (0.90–1.18)
152 obs / 147.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.83 (0.52–1.37)
0≤0.351.4
Missense OE?1.03 (0.90–1.18)
0≤0.61.4
Synonymous OE?0.81
0≤1.21.6
LoF obs/exp: 11 / 13.3Missense obs/exp: 152 / 147.7Syn Z: 1.09

This gene — mechanism propensity

DN
0.6649th %ile
GOF
0.3986th %ile
LOF
0.3452th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

856 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2
Likely Pathogenic15
VUS540
Likely Benign230
Benign16
Conflicting50
2
Pathogenic
15
Likely Pathogenic
540
VUS
230
Likely Benign
16
Benign
50
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
0
0
2
Likely Pathogenic
14
1
0
0
15
VUS
39
469
29
3
540
Likely Benign
0
13
49
168
230
Benign
0
1
15
0
16
Conflicting
—50
Total5548493171853

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

77 pathogenic / likely-pathogenic (of 106) ClinVar copy-number / structural variants overlap XRCC2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

XRCC2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients