DTNA

dystrobrevin alpha, the group of Zinc fingers ZZ-type

Basic information

Region (hg38): 18:34493291-34891844

Links

ENSG00000134769 ∙ NCBI:1837 ∙ OMIM:601239 ∙ HGNC:3057 ∙ Uniprot:Q9Y4J8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• left ventricular noncompaction 1 (Limited), mode of inheritance: AD
• Meniere disease (Limited), mode of inheritance: AD
• left ventricular noncompaction 1 (Limited), mode of inheritance: AD
• dilated cardiomyopathy (Limited), mode of inheritance: AD
• congenital heart disease (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Left ventricular noncompaction 1; Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 2	AD	Cardiovascular; Musculoskeletal	Left ventricular noncompaction 1 may affect cardiac function and may include arrhythmias, and surveillance (eg, with echocardiography and EKG), preventive measures, and medical management may be beneficial to decrease morbidity; Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 2 can involve exercise intolerance, and some individuals have been described with rhabdomyolysis, and awareness may enable preventative measures and treatment of sequelae	Cardiovascular; Musculoskeletal	11238270; 16427346; 36799992

ClinVar

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

• Left_ventricular_noncompaction_1 (485 variants)
• not_specified (138 variants)
• not_provided (134 variants)
• DTNA-related_disorder (30 variants)
• Primary_dilated_cardiomyopathy (7 variants)
• Left_ventricular_noncompaction_cardiomyopathy (4 variants)
• Cardiomyopathy (3 variants)
• Primary_familial_hypertrophic_cardiomyopathy (3 variants)
• Hypertrophic_cardiomyopathy (2 variants)
• Systolic_heart_failure (1 variants)
• Congenital_heart_disease (1 variants)
• MYOPATHY_WITH_MYALGIA,_INCREASED_SERUM_CREATINE_KINASE,_WITHOUT_EPISODIC_RHABDOMYOLYSIS_2 (1 variants)
• Meniere_disease (1 variants)
• See_cases (1 variants)
• Myopathy_with_myalgia,_increased_serum_creatine_kinase,_and_with_or_without_episodic_rhabdomyolysis_2 (1 variants)
• Cardiac_arrhythmia (1 variants)
• Dilated_cardiomyopathy_1HH (1 variants)
• Noncompaction_cardiomyopathy (1 variants)
• Ventricular_tachycardia (1 variants)
• Myopathy_with_myalgia,_increased_serum_creatine_kinase,_and_with_or_without_episodic_rhabdomyolysis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DTNA gene is commonly pathogenic or not. These statistics are base on transcript: NM_001386795.1. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	118	6	130
missense	1	2	257	17	2	279
nonsense			5			5
start loss						0
frameshift		1	4			5
splice donor/acceptor (+/-2bp)			7			7
Total	1	3	279	135	8

Highest pathogenic variant AF is 0.00000929374

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DTNA	protein_coding	protein_coding	ENST00000598334	18	398555

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.635	0.365	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.42	327	408	0.802	0.0000237	4758
Missense in Polyphen		86	140.92	0.61029		1749
Synonymous	0.0106	152	152	0.999	0.00000880	1395
Loss of Function	4.78	9	42.7	0.211	0.00000235	472

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000271	0.000271
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000704	0.0000703
Middle Eastern	0.000163	0.000163
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in the formation and stability of synapses as well as being involved in the clustering of nicotinic acetylcholine receptors.
• Disease: DISEASE: Left ventricular non-compaction 1 (LVNC1) [MIM:604169]: A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC1 is an autosomal dominant condition. {ECO:0000269|PubMed:11238270}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.204

Intolerance Scores

• loftool: 0.180
• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.65

Haploinsufficiency Scores

• pHI: 0.923
• hipred: Y
• hipred_score: 0.716
• ghis: 0.566

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.842

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dtna
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; muscle 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); growth/size/body region phenotype

Gene ontology

• Biological process: striated muscle contraction;signal transduction;chemical synaptic transmission;neuromuscular synaptic transmission
• Cellular component: cytoplasm;cell junction;axon;extrinsic component of cytoplasmic side of plasma membrane;protein-containing complex;sarcolemma;synapse
• Molecular function: protein binding;zinc ion binding;PDZ domain binding