DYNC1I2

Chr 2AR

dynein cytoplasmic 1 intermediate chain 2

Also known as: DIC74, DNCI2, IC2, NEDMIBA

NCBI Gene: 1781ENSG00000077380UniProt: Q13409

This gene encodes a member of the dynein intermediate chain family. The encoded protein is a non-catalytic component of the cytoplasmic dynein 1 complex, which acts as a retrograde microtubule motor to transport organelles and vesicles. A pseudogene of this gene is located on chromosome 10. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with microcephaly and structural brain anomaliesMIM #618492
AR
0
Active trials
27
Pathogenic / LP
123
ClinVar variants
1
Pubs (1 yr)
2.5
Missense Z
0.77
LOEUF
Clinical Summary— DYNC1I2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 82 VUS of 123 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.77LOEUF
pLI 0.000
Z-score 2.66
OE 0.52 (0.36–0.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.45Z-score
OE missense 0.61 (0.55–0.69)
195 obs / 318.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.52 (0.36–0.77)
0≤0.351.4
Missense OE0.61 (0.55–0.69)
0≤0.61.4
Synonymous OE0.87
0≤1.21.6
LoF obs/exp: 19 / 36.3Missense obs/exp: 195 / 318.0Syn Z: 1.03
DN
DN
0.6648th %ile
GOF
0.4973th %ile
LOF
0.4331th %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

123 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic1
VUS82
Likely Benign10
Benign4
26
Pathogenic
1
Likely Pathogenic
82
VUS
10
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
24
0
26
Likely Pathogenic
1
0
0
0
1
VUS
1
74
7
0
82
Likely Benign
0
2
1
7
10
Benign
0
0
4
0
4
Total377367123

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

View in ClinVar →

DYNC1I2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

DYNC1I2-related neurodevelopmental disorder with microcephaly and structural brain anomalies

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
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 2 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