DYNC2I2

dynein 2 intermediate chain 2, the group of Cilia and flagella associated|WD repeat domain containing|Dynein 2 complex subunits

Basic information

Region (hg38): 9:128633653-128656847

Previous symbols: [ "WDR34" ]

Links

ENSG00000119333 ∙ NCBI:89891 ∙ OMIM:613363 ∙ HGNC:28296 ∙ Uniprot:Q96EX3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• short-rib thoracic dysplasia 11 with or without polydactyly (Moderate), mode of inheritance: AR
• Jeune syndrome (Supportive), mode of inheritance: AR
• short rib-polydactyly syndrome, Verma-Naumoff type (Supportive), mode of inheritance: AR
• short-rib thoracic dysplasia 11 with or without polydactyly (Strong), mode of inheritance: AR
• short-rib thoracic dysplasia 11 with or without polydactyly (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Short -rib thoracic dysplasia 11 with or without polydactyly	AR	General	Genetic knowledge may potentially be beneficial related to manifestations such as renal issues; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Ophthalmologic; Renal	24183449; 24183451

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DYNC2I2 gene.

• Short-rib_thoracic_dysplasia_11_with_or_without_polydactyly (453 variants)
• Inborn_genetic_diseases (98 variants)
• not_provided (62 variants)
• DYNC2I2-related_disorder (18 variants)
• Retinal_dystrophy (8 variants)
• Jeune_thoracic_dystrophy (5 variants)
• not_specified (3 variants)
• Asphyxiating_thoracic_dystrophy_3 (2 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DYNC2I2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000052844.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	133	7	142
missense	3	8	229	10	2	252
nonsense	4	1				5
start loss						0
frameshift	19	7	1			27
splice donor/acceptor (+/-2bp)	1	4				5
Total	27	20	232	143	9

Highest pathogenic variant AF is 0.00012341529

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DYNC2I2	protein_coding	protein_coding	ENST00000372715	9	23127

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.73e-7	0.867	125633	0	108	125741	0.000430

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.122	325	319	1.02	0.0000199	3375
Missense in Polyphen		76	72.341	1.0506		802
Synonymous	-1.98	179	148	1.21	0.0000103	1132
Loss of Function	1.59	14	22.0	0.635	0.00000112	220

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000758	0.000751
Ashkenazi Jewish	0.00	0.00
East Asian	0.000387	0.000381
Finnish	0.000517	0.000508
European (Non-Finnish)	0.000490	0.000484
Middle Eastern	0.000387	0.000381
South Asian	0.000436	0.000425
Other	0.000657	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Critical for ciliary functions, essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-motor-based intraflagellar transport (IFT) machinery. Acts as a negative regulator of the Toll-like and IL-1R receptor signaling pathways. Inhibits the MAP3K7-induced NF-kappa-B activation pathway. Inhibits MAP3K7 phosphorylation at 'Thr-184' and 'Thr-187' upon Il-1 beta stimulation. {ECO:0000269|PubMed:19521662, ECO:0000269|PubMed:24183449}.
• Pathway: Intraflagellar transport;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.101

Intolerance Scores

• loftool: 0.779
• rvis_EVS: -0.66
• rvis_percentile_EVS: 15.91

Haploinsufficiency Scores

• pHI: 0.123
• hipred: N
• hipred_score: 0.177
• ghis: 0.564

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.601

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Wdr34

Zebrafish Information Network

• Gene name: wdr34
• Affected structure: photoreceptor cell
• Phenotype tag: abnormal
• Phenotype quality: swollen

Gene ontology

• Biological process: microtubule-based movement;intraciliary transport involved in cilium assembly;intraciliary transport;cilium assembly
• Cellular component: centriole;cytosol;cytoplasmic dynein complex;cilium;axoneme;dynein complex;ciliary basal body;ciliary plasm;ciliary tip
• Molecular function: protein binding;ATP-dependent microtubule motor activity, plus-end-directed;dynein light chain binding;dynein heavy chain binding