DYNC2I1

Chr 7AR

dynein 2 intermediate chain 1

Also known as: CFAP163, DIC6, FAP163, SRPS6, SRTD8, WDR60

NCBI Gene: 55112 ENSG00000126870 UniProt: Q8WVS4 OMIM: 615462

The protein functions as a non-catalytic component of the cytoplasmic dynein 2 complex, driving retrograde ciliary protein trafficking within cilia and flagella and maintaining the ciliary transition zone. Mutations cause short-rib thoracic dysplasia 8 with or without polydactyly, a skeletal ciliopathy affecting thoracic development and limb formation. Inheritance is autosomal recessive.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD) and may facilitate the formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes including cell cycle progression, signal transduction, apoptosis, and gene regulation. The encoded protein contains four WD repeats and may play a role in the formation of cilia. Mutations in this gene have been associated with short-rib polydactyly and Jeune syndromes. [provided by RefSeq, Mar 2014]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Short-rib thoracic dysplasia 8 with or without polydactylyMIM #615503

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · short-rib thoracic dysplasia 8 with or without polydactyly · AR · ClinGen 2024

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

0.67

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.67LOEUF

pLI 0.000

Z-score 3.66

OE 0.49 (0.36–0.67)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.42Z-score

OE missense 0.95 (0.89–1.02)

548 obs / 576.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.36–0.67)

0≤0.351.4

Missense OE?0.95 (0.89–1.02)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 29 / 59.5Missense obs/exp: 548 / 576.5Syn Z: 0.86

Background carrier burden — how many people carry a rare variant somewhere in DYNC2I1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 36

1,386 rare PASS variants

Rare truncating (LoF)

1 in 610

207 rare PASS variants

Rare synonymous (reference)

1 in 84

532 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DYNC2I1. 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 53	1 in 840
South Asian	~43k	1 in 42	1 in 630
Remaining (unassigned)	~30k	1 in 27	1 in 540
European (Finnish)	~27k	1 in 110	1 in 2,400
Admixed American	~22k	1 in 33	1 in 580
African / African American	~21k	1 in 35	1 in 150
East Asian	~20k	1 in 46	1 in 430
Ashkenazi Jewish	~13k	1 in 150	1 in 870
Middle Eastern	~2,884	1 in 40	≈ 1 in 580

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 21 of 25 coding exons well covered in gnomAD exomes; exons 1, 4, 9, 20 marginal. Genomes: all 25.? see exons ↓