DNM2

dynamin 2, the group of Pleckstrin homology domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 19:10718054-10833488

Links

ENSG00000079805 ∙ NCBI:1785 ∙ OMIM:602378 ∙ HGNC:2974 ∙ Uniprot:P50570 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant centronuclear myopathy (Moderate), mode of inheritance: AD
• Charcot-Marie-Tooth disease dominant intermediate B (Moderate), mode of inheritance: AD
• fetal akinesia-cerebral and retinal hemorrhage syndrome (Limited), mode of inheritance: AR
• Charcot-Marie-Tooth disease dominant intermediate B (Supportive), mode of inheritance: AD
• autosomal dominant centronuclear myopathy (Supportive), mode of inheritance: AD
• autosomal dominant Charcot-Marie-Tooth disease type 2M (Supportive), mode of inheritance: AD
• fetal akinesia-cerebral and retinal hemorrhage syndrome (Supportive), mode of inheritance: AR
• hereditary spastic paraplegia (Limited), mode of inheritance: AD
• fetal akinesia-cerebral and retinal hemorrhage syndrome (Limited), mode of inheritance: AR
• Charcot-Marie-Tooth disease dominant intermediate B (Strong), mode of inheritance: AD
• autosomal dominant centronuclear myopathy (Strong), mode of inheritance: AD
• Charcot-Marie-Tooth disease (Definitive), mode of inheritance: AD
• autosomal dominant centronuclear myopathy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Charcot-Marie-Tooth disease, dominant intermediate B; Charcot-Marie-Tooth disease, axonal, type 2M; Myopathy, centronuclear, 1; Lethal congenital contracture syndrome 5	AD/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	Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	11533912; 12481986; 12761657; 16227997; 15731758; 17932957; 18560793; 19122038; 20817456; 21221624; 22091729; 22396310; 22613877; 22924779; 23092955
Neutropenia has been described in several individuals

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNM2 gene.

• Charcot-Marie-Tooth disease dominant intermediate B (930 variants)
• not provided (274 variants)
• Inborn genetic diseases (152 variants)
• Autosomal dominant centronuclear myopathy (116 variants)
• not specified (101 variants)
• Centronuclear myopathy (13 variants)
• Charcot-Marie-Tooth disease (4 variants)
• Charcot-Marie-Tooth, Intermediate (3 variants)
• Centronuclear Myopathy, Dominant (3 variants)
• Severe X-linked myotubular myopathy (2 variants)
• DNM2-related condition (2 variants)
• Autosomal dominant centronuclear myopathy;Charcot-Marie-Tooth disease dominant intermediate B;Fetal akinesia-cerebral and retinal hemorrhage syndrome (2 variants)
• Charcot-Marie-Tooth disease dominant intermediate B;Fetal akinesia-cerebral and retinal hemorrhage syndrome;Autosomal dominant centronuclear myopathy (2 variants)
• Peripheral neuropathy (1 variants)
• Fetal akinesia-cerebral and retinal hemorrhage syndrome;Autosomal dominant Charcot-Marie-Tooth disease type 2M;Autosomal dominant centronuclear myopathy;Charcot-Marie-Tooth disease dominant intermediate B (1 variants)
• See cases (1 variants)
• Charcot-Marie-Tooth disease dominant intermediate B;Autosomal dominant centronuclear myopathy;Fetal akinesia-cerebral and retinal hemorrhage syndrome (1 variants)
• Sensorimotor neuropathy (1 variants)
• Abnormality of the musculature (1 variants)
• Charcot-Marie-Tooth disease, dominant intermediate B, with neutropenia (1 variants)
• Autosomal dominant Charcot-Marie-Tooth disease type 2M (1 variants)
• Fetal akinesia-cerebral and retinal hemorrhage syndrome;Charcot-Marie-Tooth disease dominant intermediate B;Autosomal dominant centronuclear myopathy (1 variants)
• Myofibrillar myopathy;Limb-girdle muscle weakness (1 variants)
• Fetal akinesia-cerebral and retinal hemorrhage syndrome (1 variants)
• Myopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNM2 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			10	258	3	271
missense	11	17	378	12	2	420
nonsense			4			4
start loss			1			1
frameshift			10			10
inframe indel			9			9
splice donor/acceptor (+/-2bp)			3			3
splice region			32	49	4	85
non coding			24	167	33	224
Total	11	17	439	437	38

Highest pathogenic variant AF is 0.00000657

Variants in DNM2

This is a list of pathogenic ClinVar variants found in the DNM2 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-10718090-G-T		Autosomal dominant centronuclear myopathy • Charcot-Marie-Tooth disease dominant intermediate B	Uncertain significance (Jan 13, 2018)
19-10718121-G-A		Autosomal dominant centronuclear myopathy • Charcot-Marie-Tooth disease dominant intermediate B	Uncertain significance (Jan 13, 2018)
19-10718127-C-T		Autosomal dominant centronuclear myopathy • Charcot-Marie-Tooth disease dominant intermediate B	Uncertain significance (Jan 12, 2018)
19-10718195-GC-TTGAGGGTCGCCCG		not specified	Likely benign (Oct 20, 2016)
19-10718216-GCGCTCGGGCCGGGGGCCGCCGGCGCCATGGGCAAC-G		Charcot-Marie-Tooth disease dominant intermediate B	Uncertain significance (Nov 13, 2023)
19-10718224-G-T		Autosomal dominant centronuclear myopathy • Charcot-Marie-Tooth disease dominant intermediate B	Uncertain significance (Jan 13, 2018)
19-10718245-G-T		Charcot-Marie-Tooth disease dominant intermediate B	Uncertain significance (Mar 05, 2022)
19-10718246-G-A		Autosomal dominant centronuclear myopathy	Uncertain significance (Sep 28, 2018)
19-10718247-G-A		Charcot-Marie-Tooth disease dominant intermediate B • Inborn genetic diseases	Uncertain significance (Apr 24, 2023)
19-10718250-A-G		Charcot-Marie-Tooth disease dominant intermediate B • Inborn genetic diseases	Uncertain significance (Dec 02, 2022)
19-10718252-C-T		Charcot-Marie-Tooth disease dominant intermediate B	Uncertain significance (Sep 01, 2022)
19-10718258-A-G		Charcot-Marie-Tooth disease dominant intermediate B	Uncertain significance (Jun 03, 2022)
19-10718261-G-C		Charcot-Marie-Tooth disease dominant intermediate B	Uncertain significance (Mar 01, 2020)
19-10718262-A-G		Charcot-Marie-Tooth disease dominant intermediate B	Uncertain significance (Sep 13, 2022)
19-10718272-C-T		Charcot-Marie-Tooth disease dominant intermediate B	Likely benign (Oct 13, 2022)
19-10718273-C-T		Charcot-Marie-Tooth disease dominant intermediate B • Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
19-10718274-C-T			Uncertain significance (Apr 12, 2023)
19-10718275-G-A		Charcot-Marie-Tooth disease dominant intermediate B • Inborn genetic diseases	Likely benign (Oct 03, 2023)
19-10718275-G-T		Charcot-Marie-Tooth disease dominant intermediate B	Likely benign (Nov 08, 2022)
19-10718276-C-G		Inborn genetic diseases	Uncertain significance (Sep 13, 2019)
19-10718279-G-A		Charcot-Marie-Tooth disease dominant intermediate B	Uncertain significance (Aug 10, 2023)
19-10718279-G-C		Autosomal dominant centronuclear myopathy	Uncertain significance (Sep 19, 2023)
19-10718283-A-G		Charcot-Marie-Tooth disease dominant intermediate B	Uncertain significance (Jun 13, 2022)
19-10718286-A-G			Uncertain significance (Nov 20, 2020)
19-10718287-A-G		Charcot-Marie-Tooth disease dominant intermediate B	Likely benign (Jul 22, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNM2	protein_coding	protein_coding	ENST00000389253	21	115410

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000248	125731	0	5	125736	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.48	302	527	0.573	0.0000374	5696
Missense in Polyphen		85	218.55	0.38894		2303
Synonymous	-2.09	260	220	1.18	0.0000166	1731
Loss of Function	5.66	3	43.1	0.0696	0.00000241	484

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000471	0.0000462
European (Non-Finnish)	0.0000184	0.0000176
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Microtubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP. Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones (By similarity). Plays an important role in vesicular trafficking processes, in particular endocytosis. Involved in cytokinesis (PubMed:12498685). Regulates maturation of apoptotic cell corpse-containing phagosomes by recruiting PIK3C3 to the phagosome membrane (By similarity). {ECO:0000250|UniProtKB:P39052, ECO:0000250|UniProtKB:P39054, ECO:0000269|PubMed:12498685}.
• Disease: DISEASE: Myopathy, centronuclear, 1 (CNM1) [MIM:160150]: A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. {ECO:0000269|PubMed:16227997, ECO:0000269|PubMed:17825552, ECO:0000269|PubMed:17932957, ECO:0000269|PubMed:19122038, ECO:0000269|PubMed:19623537, ECO:0000269|PubMed:19932619, ECO:0000269|PubMed:19932620, ECO:0000269|PubMed:20227276, ECO:0000269|PubMed:22396310}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Lethal congenital contracture syndrome 5 (LCCS5) [MIM:615368]: A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. {ECO:0000269|PubMed:23092955}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease, dominant, intermediate type, B (CMTDIB) [MIM:606482]: A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. The dominant intermediate type B is characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. {ECO:0000269|PubMed:15731758, ECO:0000269|PubMed:19623537}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease 2M (CMT2M) [MIM:606482]: An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269|PubMed:17636067, ECO:0000269|PubMed:18560793}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fc gamma R-mediated phagocytosis - Homo sapiens (human);Synaptic vesicle cycle - Homo sapiens (human);Endocytosis - Homo sapiens (human);Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Synaptic Vesicle Pathway;Developmental Biology;Golgi Associated Vesicle Biogenesis;Lysosome Vesicle Biogenesis;Clathrin derived vesicle budding;trans-Golgi Network Vesicle Budding;Signal Transduction;Recycling pathway of L1;Vesicle-mediated transport;Membrane Trafficking;Prolactin;Metabolism of nitric oxide;Toll-Like Receptors Cascades;MHC class II antigen presentation;TCR;NOSTRIN mediated eNOS trafficking;eNOS activation and regulation;Purine metabolism;Innate Immune System;Immune System;Metabolism;Adaptive Immune System;Retrograde neurotrophin signalling;Clathrin-mediated endocytosis;Signaling by NTRK1 (TRKA);Signaling by NTRKs;Posttranslational regulation of adherens junction stability and dissassembly;Arf6 trafficking events;L1CAM interactions;Axon guidance;IL5;Toll Like Receptor 4 (TLR4) Cascade;Signaling by Receptor Tyrosine Kinases;Formation of annular gap junctions;Gap junction degradation;Gap junction trafficking;Gap junction trafficking and regulation;PAR1-mediated thrombin signaling events;PDGFR-beta signaling pathway;Syndecan-4-mediated signaling events;Signaling events mediated by VEGFR1 and VEGFR2 (Consensus)

Recessive Scores

• pRec: 0.674

Intolerance Scores

• loftool: 0.113
• rvis_EVS: -1.33
• rvis_percentile_EVS: 4.71

Haploinsufficiency Scores

• pHI: 0.133
• hipred: Y
• hipred_score: 0.775
• ghis: 0.621

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dnm2
• 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); normal phenotype; digestive/alimentary 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; renal/urinary system phenotype; growth/size/body region phenotype; muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: dnm2a
• Affected structure: cardiac muscle cell
• Phenotype tag: abnormal
• Phenotype quality: vacuolated

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;G protein-coupled receptor internalization;ventricular septum development;regulation of transcription, DNA-templated;Golgi to plasma membrane transport;endocytosis;receptor-mediated endocytosis;phagocytosis;signal transduction;spermatogenesis;response to light stimulus;positive regulation of lamellipodium assembly;synaptic vesicle budding from presynaptic endocytic zone membrane;antigen processing and presentation of exogenous peptide antigen via MHC class II;negative regulation of transforming growth factor beta receptor signaling pathway;regulation of axon extension;receptor internalization;transferrin transport;regulation of Rac protein signal transduction;aorta development;response to cocaine;positive regulation of apoptotic process;macropinocytosis;positive regulation of nitric oxide biosynthetic process;positive regulation of transcription, DNA-templated;synaptic vesicle transport;neuron projection morphogenesis;positive regulation of phagocytosis;regulation of synapse structure or activity;regulation of nitric-oxide synthase activity;coronary vasculature development;membrane organization;cellular response to carbon monoxide;cellular response to X-ray;cellular response to nitric oxide;postsynaptic neurotransmitter receptor internalization;positive regulation of substrate adhesion-dependent cell spreading;negative regulation of non-motile cilium assembly;cellular response to dopamine;regulation of Golgi organization;positive regulation of sodium:potassium-exchanging ATPase activity;negative regulation of membrane tubulation;positive regulation of clathrin-dependent endocytosis
• Cellular component: Golgi membrane;phagocytic cup;photoreceptor inner segment;nucleus;cytoplasm;endosome;Golgi apparatus;trans-Golgi network;centrosome;cytosol;microtubule;plasma membrane;clathrin-coated pit;focal adhesion;postsynaptic density;membrane;lamellipodium;axon;growth cone;midbody;endocytic vesicle membrane;phagocytic vesicle membrane;cytoplasmic vesicle;ruffle membrane;protein-containing complex;dendritic spine;dendritic spine head;synapse;postsynaptic membrane;clathrin-coated endocytic vesicle;perinuclear region of cytoplasm;extracellular exosome;presynapse;postsynaptic endocytic zone membrane;glutamatergic synapse;postsynaptic density, intracellular component
• Molecular function: GTPase activity;protein binding;GTP binding;microtubule binding;SH3 domain binding;enzyme binding;protein kinase binding;D2 dopamine receptor binding;phosphatidylinositol 3-kinase regulatory subunit binding;protein-containing complex binding;WW domain binding;nitric-oxide synthase binding