DYNC1I2

Chr 2AR

dynein cytoplasmic 1 intermediate chain 2

Also known as: DIC74, DNCI2, IC2, NEDMIBA

NCBI Gene: 1781 ENSG00000077380 UniProt: Q13409 OMIM: 603331

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with microcephaly and structural brain anomaliesMIM #618492

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Neurodevelopmental disorder with microcephaly and structural brain anomalies; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.77

LOEUF

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in DYNC1I2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

541 rare PASS variants

Rare truncating (LoF)

1 in 490

102 rare PASS variants

Rare synonymous (reference)

1 in 250

225 rare PASS variants

Rare missense and truncating variants are carried at similar rates in DYNC1I2; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 540
South Asian	~43k	1 in 90	1 in 310
Remaining (unassigned)	~30k	1 in 110	1 in 380
European (Finnish)	~27k	1 in 310	1 in 1,000
Admixed American	~22k	1 in 110	1 in 310
African / African American	~21k	1 in 97	1 in 540
East Asian	~20k	1 in 210	1 in 490
Ashkenazi Jewish	~13k	1 in 460	1 in 270
Middle Eastern	~2,884	1 in 92	1 in 400

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 15 of 17 coding exons well covered in gnomAD exomes; exons 8, 13 marginal. Genomes: 16 of 17 (exon 8 below).? see exons ↓