DYNC1I2

dynein cytoplasmic 1 intermediate chain 2, the group of WD repeat domain containing|Dynein 1 complex subunits

Basic information

Region (hg38): 2:171687409-171750158

Previous symbols: [ "DNCI2" ]

Links

ENSG00000077380 ∙ NCBI:1781 ∙ OMIM:603331 ∙ HGNC:2964 ∙ Uniprot:Q13409 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with microcephaly and structural brain anomalies (Strong), mode of inheritance: AR
• neurodevelopmental disorder with microcephaly and structural brain anomalies (Limited), mode of inheritance: AR
• neurodevelopmental disorder with microcephaly and structural brain anomalies (Strong), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DYNC1I2 gene.

• Neurodevelopmental disorder with microcephaly and structural brain anomalies (2 variants)
• Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (2 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DYNC1I2 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				5		5
missense	1		32	2		35
nonsense	2		1			3
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1	1			2
splice region			1	1	3	5
non coding			1		1	2
Total	3	1	35	7	1

Highest pathogenic variant AF is 0.00000665

Variants in DYNC1I2

This is a list of pathogenic ClinVar variants found in the DYNC1I2 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-171690183-G-A		not specified	Uncertain significance (Oct 20, 2024)
2-171690204-C-T			Pathogenic (Dec 01, 2022)
2-171690205-G-A		not specified	Uncertain significance (Nov 10, 2024)
2-171690263-A-T			Uncertain significance (Dec 01, 2022)
2-171692782-C-G		not specified	Uncertain significance (May 23, 2023)
2-171692812-A-C		not specified	Uncertain significance (Mar 22, 2024)
2-171692825-C-T		not specified	Uncertain significance (Nov 21, 2024)
2-171692888-C-G		not specified	Uncertain significance (Apr 07, 2022)
2-171692892-T-C		not specified	Uncertain significance (Oct 06, 2023)
2-171707268-T-G		Neurodevelopmental disorder with microcephaly and structural brain anomalies	Uncertain significance (Jul 06, 2023)
2-171707308-C-G		not specified	Uncertain significance (Jun 03, 2022)
2-171707348-A-G			Likely benign (Jan 01, 2024)
2-171712769-C-T		not specified	Uncertain significance (Mar 02, 2023)
2-171712785-A-G			Likely benign (Feb 01, 2024)
2-171712793-C-A			Uncertain significance (May 05, 2022)
2-171715328-A-G		not specified	Likely benign (Dec 04, 2024)
2-171715330-G-A		not specified	Uncertain significance (Mar 22, 2024)
2-171715396-C-T		not specified	Uncertain significance (Jan 26, 2023)
2-171715444-G-A			Uncertain significance (Nov 03, 2021)
2-171725598-GTT-G		DYNC1I2-related disorder	Benign (Nov 19, 2019)
2-171725598-G-GT		DYNC1I2-related disorder	Benign (Mar 11, 2024)
2-171725598-G-GTT		DYNC1I2-related disorder	Benign (Nov 25, 2019)
2-171725602-T-G		not specified	Benign (Mar 28, 2016)
2-171725615-C-A		DYNC1I2-related disorder	Likely benign (Dec 06, 2019)
2-171725629-G-T		not specified	Uncertain significance (Jan 03, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DYNC1I2	protein_coding	protein_coding	ENST00000397119	17	61012

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.06e-8	0.997	124890	0	52	124942	0.000208

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.45	195	318	0.613	0.0000161	4170
Missense in Polyphen		33	72.603	0.45452		889
Synonymous	1.03	93	107	0.873	0.00000544	1179
Loss of Function	2.66	19	36.3	0.524	0.00000192	453

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000322	0.000321
Ashkenazi Jewish	0.000895	0.000895
East Asian	0.000167	0.000164
Finnish	0.000336	0.000324
European (Non-Finnish)	0.000202	0.000194
Middle Eastern	0.000167	0.000164
South Asian	0.000139	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. The intermediate chains mediate the binding of dynein to dynactin via its 150 kDa component (p150- glued) DCNT1. Involved in membrane-transport, such as Golgi apparatus, late endosomes and lysosomes.
• Pathway: Salmonella infection - Homo sapiens (human);Phagosome - Homo sapiens (human);Vasopressin-regulated water reabsorption - Homo sapiens (human);Signal Transduction;Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Amplification of signal from the kinetochores;Mitotic Spindle Checkpoint;Cell Cycle Checkpoints;RHO GTPases Activate Formins;RHO GTPase Effectors;Signaling by Rho GTPases;Regulation of PLK1 Activity at G2/M Transition;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;COPI-independent Golgi-to-ER retrograde traffic;Golgi-to-ER retrograde transport;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;COPI-mediated anterograde transport;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Resolution of Sister Chromatid Cohesion;ER to Golgi Anterograde Transport;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Intra-Golgi and retrograde Golgi-to-ER traffic;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.199

Intolerance Scores

• loftool: 0.741
• rvis_EVS: -0.58
• rvis_percentile_EVS: 18.44

Haploinsufficiency Scores

• pHI: 0.214
• hipred: Y
• hipred_score: 0.715
• ghis: 0.657

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.909

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dync1i2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;endoplasmic reticulum to Golgi vesicle-mediated transport;microtubule-based movement;regulation of G2/M transition of mitotic cell cycle;viral process;antigen processing and presentation of exogenous peptide antigen via MHC class II;ciliary basal body-plasma membrane docking
• Cellular component: cytoplasm;centrosome;cytosol;cytoplasmic dynein complex;microtubule;dynein complex;vesicle
• Molecular function: microtubule motor activity;protein binding;ATP-dependent microtubule motor activity, plus-end-directed;dynein light chain binding;dynein heavy chain binding