DYNC2H1

dynein cytoplasmic 2 heavy chain 1, the group of Dynein 2 complex subunits

Basic information

Region (hg38): 11:103109410-103479863

Previous symbols: [ "DNCH2" ]

Links

ENSG00000187240 ∙ NCBI:79659 ∙ OMIM:603297 ∙ HGNC:2962 ∙ Uniprot:Q8NCM8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• asphyxiating thoracic dystrophy 3 (Definitive), mode of inheritance: AR
• asphyxiating thoracic dystrophy 3 (Definitive), mode of inheritance: AR
• Jeune syndrome (Supportive), mode of inheritance: AR
• short rib-polydactyly syndrome, Majewski type (Supportive), mode of inheritance: AR
• asphyxiating thoracic dystrophy 3 (Supportive), mode of inheritance: AR
• short rib-polydactyly syndrome, Verma-Naumoff type (Supportive), mode of inheritance: AR
• asphyxiating thoracic dystrophy 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Short-rib thoracic dysplasia 3 with or without polydactyly	AR/Digenic	General	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	Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	19442771; 19361615; 21211617; 22499340; 22791528; 22499340
Digenic variants in both NEK1 and DYNC2H1 can result in disease

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DYNC2H1 gene.

• Jeune thoracic dystrophy (192 variants)
• Asphyxiating thoracic dystrophy 3 (30 variants)
• not provided (23 variants)
• DYNC2H1-related disorder (3 variants)
• Autosomal recessive polycystic kidney disease (1 variants)
• not specified (1 variants)
• Short-rib thoracic dysplasia 6 with or without polydactyly (1 variants)
• Narrow chest;Fetal growth restriction;Bowing of the long bones (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DYNC2H1 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			13	874	15	902
missense	2	50	663	38	6	759
nonsense	103	19	1			123
start loss	1		2			3
frameshift	87	13				100
inframe indel	1		5			6
splice donor/acceptor (+/-2bp)	11	72			1	84
splice region	1	2	34	196	18	251
non coding		1	12	681	270	964
Total	205	155	696	1593	292

Highest pathogenic variant AF is 0.000138

Variants in DYNC2H1

This is a list of pathogenic ClinVar variants found in the DYNC2H1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-103109427-T-C		Asphyxiating thoracic dystrophy 3	Uncertain significance (Jan 13, 2018)
11-103109481-G-T		Asphyxiating thoracic dystrophy 3 • Jeune thoracic dystrophy	Benign/Likely benign (Jun 26, 2018)
11-103109535-C-T		not specified	Likely benign (Jan 04, 2018)
11-103109542-C-T		Asphyxiating thoracic dystrophy 3 • Jeune thoracic dystrophy	Uncertain significance (Jan 12, 2018)
11-103109575-A-G		Jeune thoracic dystrophy	Uncertain significance (Jun 23, 2022)
11-103109575-AT-A		Jeune thoracic dystrophy	Uncertain significance (Nov 06, 2019)
11-103109576-T-C		Asphyxiating thoracic dystrophy 3	Pathogenic (Apr 01, 2022)
11-103109583-C-T		Jeune thoracic dystrophy	Likely benign (Sep 24, 2023)
11-103109589-T-C		Jeune thoracic dystrophy	Likely benign (Apr 12, 2023)
11-103109595-C-T		Asphyxiating thoracic dystrophy 3 • Jeune thoracic dystrophy • not specified	Benign/Likely benign (Feb 01, 2024)
11-103109601-G-T		Jeune thoracic dystrophy • Asphyxiating thoracic dystrophy 3	Benign (Jan 31, 2024)
11-103109607-C-T		Short rib-polydactyly syndrome • Jeune thoracic dystrophy • Asphyxiating thoracic dystrophy 3	Conflicting classifications of pathogenicity (Jan 31, 2024)
11-103109609-T-G		Inborn genetic diseases • Jeune thoracic dystrophy	Uncertain significance (Jul 28, 2022)
11-103109617-A-T		Jeune thoracic dystrophy	Uncertain significance (Feb 11, 2022)
11-103109619-T-C		Jeune thoracic dystrophy	Likely benign (Nov 08, 2023)
11-103109625-C-A		Jeune thoracic dystrophy	Likely benign (Dec 11, 2023)
11-103109628-G-T		Jeune thoracic dystrophy	Uncertain significance (Aug 12, 2021)
11-103109634-C-T		Jeune thoracic dystrophy	Likely benign (Oct 22, 2023)
11-103109635-T-G		Asphyxiating thoracic dystrophy 3	Uncertain significance (Feb 12, 2020)
11-103109638-G-C		Jeune thoracic dystrophy	Likely benign (Jan 11, 2024)
11-103109640-G-T		Jeune thoracic dystrophy	Likely benign (Apr 30, 2023)
11-103109646-G-A		Jeune thoracic dystrophy	Uncertain significance (Jul 30, 2022)
11-103109678-A-G		Inborn genetic diseases	Uncertain significance (Jan 10, 2023)
11-103109682-T-C		Jeune thoracic dystrophy	Likely benign (Apr 30, 2023)
11-103109700-C-A		Asphyxiating thoracic dystrophy 3	Uncertain significance (Jan 04, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DYNC2H1	protein_coding	protein_coding	ENST00000398093	90	370432

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.14e-44	1.00	124350	1	287	124638	0.00116

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.909	1890	2.00e+3	0.943	0.000104	28122
Missense in Polyphen		416	557.63	0.74601		7790
Synonymous	-0.732	698	674	1.04	0.0000334	7846
Loss of Function	7.12	113	229	0.493	0.0000127	3065

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00302	0.00292
Ashkenazi Jewish	0.00132	0.00129
East Asian	0.000969	0.000946
Finnish	0.000142	0.000139
European (Non-Finnish)	0.00137	0.00123
Middle Eastern	0.000969	0.000946
South Asian	0.00132	0.00128
Other	0.00155	0.00132

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May function as a motor for intraflagellar retrograde transport. Functions in cilia biogenesis. May play a role in transport between endoplasmic reticulum and Golgi or organization of the Golgi in cells (By similarity). {ECO:0000250}.
• Disease: DISEASE: Short-rib thoracic dysplasia 3 with or without polydactyly (SRTD3) [MIM:613091]: A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. {ECO:0000269|PubMed:19361615, ECO:0000269|PubMed:19442771, ECO:0000269|PubMed:22499340, ECO:0000269|PubMed:23456818}. Note=The disease is caused by mutations affecting the gene represented in this entry. In some cases DYNC2H1 mutations result in disease phenotype in the presence of mutations in NEK1 indicating digenic inheritance (digenic short rib-polydactyly syndrome 3/6 with polydactyly) (PubMed:21211617). {ECO:0000269|PubMed:21211617}.
• Pathway: Salmonella infection - Homo sapiens (human);Phagosome - Homo sapiens (human);Vasopressin-regulated water reabsorption - Homo sapiens (human);Purine metabolism;Intraflagellar transport;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.106

Intolerance Scores

• loftool: 0.998
• rvis_EVS: -0.35
• rvis_percentile_EVS: 29.56

Haploinsufficiency Scores

• pHI: 0.120
• hipred: Y
• hipred_score: 0.652
• ghis: 0.514

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.908

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Dync2h1
• Phenotype: cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; respiratory system phenotype; renal/urinary system phenotype; skeleton phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype

Zebrafish Information Network

• Gene name: dync2h1
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: microtubule-based movement;Golgi organization;multicellular organism development;intraciliary retrograde transport;intraciliary transport involved in cilium assembly;cilium assembly
• Cellular component: Golgi apparatus;cytoplasmic dynein complex;microtubule;plasma membrane;cilium;axoneme;dynein complex;motile cilium;extracellular exosome;ciliary tip
• Molecular function: motor activity;ATP binding;ATP-dependent microtubule motor activity, minus-end-directed;dynein light chain binding;dynein intermediate chain binding;dynein light intermediate chain binding