DYNC2LI1

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

Basic information

Region (hg38): 2:43774039-43810010

Links

ENSG00000138036 ∙ NCBI:51626 ∙ OMIM:617083 ∙ HGNC:24595 ∙ Uniprot:Q8TCX1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Jeune syndrome (Supportive), mode of inheritance: AR
• Ellis-van Creveld syndrome (Supportive), mode of inheritance: AR
• short-rib thoracic dysplasia 15 with polydactyly (Definitive), mode of inheritance: AR
• short-rib thoracic dysplasia 15 with polydactyly (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Short-rib throacic dysplasia 15 with polydactyly	AR	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; Musculoskeletal	26077881; 26130459

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DYNC2LI1 gene.

• not provided (7 variants)
• Short-rib thoracic dysplasia 15 with polydactyly (6 variants)
• Asphyxiating thoracic dystrophy 1 (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DYNC2LI1 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			1	18	3	22
missense	3		53	4	8	68
nonsense	2	1				3
start loss	1					1
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)		3				3
splice region			6	6	2	14
non coding				28	28	56
Total	7	4	54	50	39

Highest pathogenic variant AF is 0.0000526

Variants in DYNC2LI1

This is a list of pathogenic ClinVar variants found in the DYNC2LI1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-43774077-C-T			Benign (May 12, 2021)
2-43774140-T-C		Short-rib thoracic dysplasia 15 with polydactyly	Pathogenic (May 06, 2022)
2-43774155-T-C			Likely benign (Jul 30, 2022)
2-43774160-C-T			Benign (Jan 16, 2024)
2-43774161-C-G			Benign (Jan 15, 2024)
2-43776769-G-A			Likely benign (Jul 19, 2022)
2-43776778-G-A			Likely benign (Jul 27, 2023)
2-43776784-A-G			Uncertain significance (May 12, 2022)
2-43776786-ACT-A		Short-rib thoracic dysplasia 15 with polydactyly	Pathogenic (May 20, 2021)
2-43776787-C-G			Uncertain significance (Aug 22, 2022)
2-43776789-C-T		Short-rib thoracic dysplasia 15 with polydactyly • DYNC2LI1-related disorder	Likely benign (Jan 29, 2024)
2-43776807-G-C			Uncertain significance (May 04, 2022)
2-43776810-G-C		Inborn genetic diseases	Uncertain significance (Jun 09, 2022)
2-43776823-G-T			Uncertain significance (Jun 20, 2021)
2-43776840-G-A		Inborn genetic diseases	Uncertain significance (Jun 02, 2023)
2-43776844-G-A			Uncertain significance (Aug 22, 2022)
2-43776871-T-C		Short-rib thoracic dysplasia 15 with polydactyly	Benign (Jan 31, 2024)
2-43776888-A-T			Uncertain significance (Jun 14, 2022)
2-43776896-T-TA		Short-rib thoracic dysplasia 15 with polydactyly	Pathogenic (Apr 06, 2018)
2-43776899-G-C			Uncertain significance (Jul 13, 2021)
2-43776910-C-CT			Benign (Jan 19, 2024)
2-43776960-T-G			Benign (May 11, 2021)
2-43783481-G-A			Benign (May 11, 2021)
2-43783500-C-G			Likely benign (Nov 10, 2023)
2-43783501-C-T			Likely benign (Sep 29, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DYNC2LI1	protein_coding	protein_coding	ENST00000260605	13	35972

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.15e-9	0.516	125683	0	59	125742	0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.326	195	183	1.07	0.00000908	2301
Missense in Polyphen		50	46.564	1.0738		579
Synonymous	0.397	60	64.0	0.937	0.00000356	620
Loss of Function	1.10	16	21.5	0.743	9.77e-7	288

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000365	0.000364
Ashkenazi Jewish	0.000595	0.000595
East Asian	0.000383	0.000381
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000302	0.000299
Middle Eastern	0.000383	0.000381
South Asian	0.0000665	0.0000653
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for correct intraflagellar transport (IFT), the bi-directional movement of particles required for the assembly, maintenance and functioning of primary cilia. Involved in the regulation of ciliary length. {ECO:0000269|PubMed:26077881, ECO:0000269|PubMed:26130459}.
• Pathway: Vasopressin-regulated water reabsorption - Homo sapiens (human);Intraflagellar transport;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.0823

Intolerance Scores

• loftool: 0.809
• rvis_EVS: 1.6
• rvis_percentile_EVS: 95.87

Haploinsufficiency Scores

• pHI: 0.0538
• hipred: N
• hipred_score: 0.471
• ghis: 0.412

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.249

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dync2li1
• Phenotype: embryo 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); 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); limbs/digits/tail phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: dync2li1
• Affected structure: photoreceptor cell
• Phenotype tag: abnormal
• Phenotype quality: vacuolated

Gene ontology

• Biological process: determination of left/right symmetry;intraciliary retrograde transport;intraciliary transport involved in cilium assembly;regulation of cilium assembly
• Cellular component: cytoplasm;centrosome;cytoplasmic dynein complex;cytoplasmic microtubule;cilium;axoneme;intraciliary transport particle;motile cilium;ciliary transition zone;ciliary basal body;apical part of cell;ciliary tip
• Molecular function: protein binding;ATP-dependent microtubule motor activity, minus-end-directed;dynein heavy chain binding