DYNC1I2

Chr 2

dynein cytoplasmic 1 intermediate chain 2

Also known as: DIC74, DNCI2, IC2, NEDMIBA

NCBI Gene: 1781 ENSG00000077380 UniProt: Q13409

This protein serves as a non-catalytic component of the cytoplasmic dynein 1 complex that transports organelles and vesicles along microtubules and links dynein to cargo proteins. Mutations cause autosomal dominant spinal muscular atrophy with lower extremity predominance, typically presenting in childhood to adulthood with progressive weakness primarily affecting the legs. The gene shows moderate constraint against loss-of-function variants.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.77

Clinical Summary— DYNC1I2

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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

5 unique Pathogenic / Likely Pathogenic· 79 VUS of 122 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.52 (0.36–0.77)

0≤0.351.4

Missense OE?0.61 (0.55–0.69)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 19 / 36.3Missense obs/exp: 195 / 318.0Syn Z: 1.03

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongDYNC1I2-related neurodevelopmental disorder with microcephaly and structural brain anomaliesLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6648th %ile

GOF

0.4973th %ile

LOF

0.4331th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

122 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic1

VUS79

Likely Benign10

Benign4

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	1	0	0	4
Likely Pathogenic	1	0	0	0	1
VUS	3	75	1	0	79
Likely Benign	0	2	1	7	10
Benign	0	0	4	0	4
Total	7	78	6	7	98

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap DYNC1I2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →