DGCR2

Chr 22

DiGeorge syndrome critical region gene 2

Also known as: DGS-C, IDD, LAN, SEZ-12

NCBI Gene: 9993ENSG00000070413UniProt: P98153OMIM: 600594

The protein functions as a putative adhesion receptor involved in cell-cell and cell-matrix interactions required for normal cell differentiation and migration. Mutations cause DiGeorge syndrome, velocardiofacial syndrome, and conotruncal anomaly face syndrome, affecting cardiac, craniofacial, and immunological development. These conditions follow an autosomal dominant inheritance pattern and are part of the 22q11.2 deletion syndrome spectrum.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 0.88
Clinical Summary— DGCR2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
260 unique Pathogenic / Likely Pathogenic· 115 VUS of 399 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.88LOEUF
pLI 0.000
Z-score 1.98
OE 0.55 (0.35–0.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.66Z-score
OE missense 0.90 (0.82–0.99)
327 obs / 362.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.55 (0.35–0.88)
0≤0.351.4
Missense OE0.90 (0.82–0.99)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 12 / 22.0Missense obs/exp: 327 / 362.6Syn Z: 0.13
DN
0.5771th %ile
GOF
0.6541th %ile
LOF
0.3746th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

399 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic257
Likely Pathogenic3
VUS115
Likely Benign4
Benign3
257
Pathogenic
3
Likely Pathogenic
115
VUS
4
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
257
0
257
Likely Pathogenic
0
0
3
0
3
VUS
0
100
15
0
115
Likely Benign
0
2
0
2
4
Benign
0
1
2
0
3
Total01032772382

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

View in ClinVar →

Protein Context — Lollipop Plot

DGCR2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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