DYNC2I1

dynein 2 intermediate chain 1, the group of Cilia and flagella associated|Dynein 2 complex subunits|WD repeat domain containing

Basic information

Region (hg38): 7:158856557-158956747

Previous symbols: [ "WDR60" ]

Links

ENSG00000126870 ∙ NCBI:55112 ∙ OMIM:615462 ∙ HGNC:21862 ∙ Uniprot:Q8WVS4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Jeune syndrome (Supportive), mode of inheritance: AR
• short rib-polydactyly syndrome, Verma-Naumoff type (Supportive), mode of inheritance: AR
• short-rib thoracic dysplasia 8 with or without polydactyly (Strong), mode of inheritance: AR
• short-rib thoracic dysplasia 8 with or without polydactyly (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Short-rib thoracic dysplasia 8 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	Cardiovascular; Gastrointestinal; Genitourinary; Musculoskeletal; Pulmonary; Renal	23910462
The condition may involve multiple malformations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DYNC2I1 gene.

• Short-rib thoracic dysplasia 8 with or without polydactyly (331 variants)
• not provided (57 variants)
• Inborn genetic diseases (18 variants)
• not specified (7 variants)
• DYNC2I1-related condition (3 variants)
• See cases (3 variants)
• Asphyxiating thoracic dystrophy 3 (2 variants)
• Jeune thoracic dystrophy (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DYNC2I1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	74	13	89
missense	1		136	15	12	164
nonsense	4	1	2			7
start loss						0
frameshift	5	2	1			8
inframe indel			3		1	4
splice donor/acceptor (+/-2bp)		1				1
splice region			7	10	4	21
non coding			3	51	39	93
Total	10	4	147	140	65

Highest pathogenic variant AF is 0.0000197

Variants in DYNC2I1

This is a list of pathogenic ClinVar variants found in the DYNC2I1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-158856569-C-T			Benign (May 19, 2021)
7-158856589-T-C			Benign (Jun 23, 2018)
7-158856606-C-T			Benign (May 20, 2021)
7-158856613-T-C			Benign (Jun 23, 2018)
7-158856643-C-T			Benign (May 26, 2021)
7-158856682-A-G			Benign (Jun 23, 2018)
7-158856746-G-T		Inborn genetic diseases	Uncertain significance (Sep 12, 2023)
7-158856754-G-A		Short-rib thoracic dysplasia 8 with or without polydactyly	Uncertain significance (Aug 11, 2021)
7-158856758-C-T		Short-rib thoracic dysplasia 8 with or without polydactyly	Likely benign (Dec 17, 2023)
7-158856762-G-C		Short-rib thoracic dysplasia 8 with or without polydactyly	Likely benign (Jan 19, 2024)
7-158856762-G-T		Short-rib thoracic dysplasia 8 with or without polydactyly	Likely benign (Nov 15, 2021)
7-158856767-G-A		Short-rib thoracic dysplasia 8 with or without polydactyly	Likely benign (Nov 21, 2021)
7-158869740-C-T			Likely benign (May 19, 2021)
7-158869820-T-TTTTAAAC			Benign (Nov 12, 2018)
7-158869842-C-T		Short-rib thoracic dysplasia 8 with or without polydactyly	Likely benign (Jul 14, 2021)
7-158869849-A-G		Short-rib thoracic dysplasia 8 with or without polydactyly	Likely benign (Aug 23, 2022)
7-158869874-C-T		Short-rib thoracic dysplasia 8 with or without polydactyly	Uncertain significance (Apr 22, 2022)
7-158869888-G-A		Short-rib thoracic dysplasia 8 with or without polydactyly	Uncertain significance (Dec 11, 2023)
7-158869908-G-A		Short-rib thoracic dysplasia 8 with or without polydactyly • not specified	Uncertain significance (Jan 15, 2024)
7-158869915-A-G		Short-rib thoracic dysplasia 8 with or without polydactyly	Likely benign (Oct 04, 2018)
7-158869923-G-A		Short-rib thoracic dysplasia 8 with or without polydactyly	Likely benign (Jan 11, 2022)
7-158870007-T-C			Benign (Jun 23, 2018)
7-158871122-C-A		Short-rib thoracic dysplasia 8 with or without polydactyly	Likely benign (May 23, 2023)
7-158871151-T-A		Inborn genetic diseases	Uncertain significance (Feb 17, 2024)
7-158871176-A-G		Short-rib thoracic dysplasia 8 with or without polydactyly	Uncertain significance (Jun 13, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DYNC2I1	protein_coding	protein_coding	ENST00000407559	25	100170

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.32e-12	1.00	124476	0	169	124645	0.000678

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.422	548	577	0.951	0.0000328	7008
Missense in Polyphen		37	61.289	0.6037		708
Synonymous	0.863	209	225	0.927	0.0000145	1949
Loss of Function	3.66	29	59.5	0.488	0.00000336	707

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00140	0.00126
Ashkenazi Jewish	0.00756	0.00758
East Asian	0.000564	0.000556
Finnish	0.00	0.00
European (Non-Finnish)	0.000365	0.000327
Middle Eastern	0.000564	0.000556
South Asian	0.000305	0.000294
Other	0.000997	0.000992

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in ciliogenesis. {ECO:0000269|PubMed:23910462}.
• Pathway: Intraflagellar transport;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.0922

Intolerance Scores

• loftool: 0.751
• rvis_EVS: 1.21
• rvis_percentile_EVS: 93.05

Haploinsufficiency Scores

• pHI: 0.112
• hipred: N
• hipred_score: 0.270
• ghis: 0.472

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.713

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wdr60

Gene ontology

• Biological process: microtubule-based movement;intraciliary transport involved in cilium assembly;embryonic skeletal system morphogenesis;cilium assembly
• Cellular component: pericentriolar material;spindle pole;extracellular space;centrosome;cytoplasmic dynein complex;cilium;dynein complex;interphase microtubule organizing center;ciliary tip;ciliary base
• Molecular function: protein binding;ATP-dependent microtubule motor activity, plus-end-directed;dynein light chain binding;dynein heavy chain binding