DNAAF3

dynein axonemal assembly factor 3, the group of Axonemal dynein assembly factors

Basic information

Region (hg38): 19:55158660-55166722

Previous symbols: [ "C19orf51", "CILD2" ]

Links

ENSG00000167646 ∙ NCBI:352909 ∙ OMIM:614566 ∙ HGNC:30492 ∙ Uniprot:Q8N9W5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary ciliary dyskinesia 2 (Definitive), mode of inheritance: AR
• primary ciliary dyskinesia 2 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia 2 (Moderate), mode of inheritance: AR
• primary ciliary dyskinesia 2 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia (Supportive), mode of inheritance: AD
• primary ciliary dyskinesia 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary, 2	AR	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary	Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Genitourinary; Pulmonary	22387996

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNAAF3 gene.

• Primary ciliary dyskinesia (321 variants)
• not provided (53 variants)
• not specified (25 variants)
• Primary ciliary dyskinesia 2 (25 variants)
• Inborn genetic diseases (23 variants)
• Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome (16 variants)
• Dilated Cardiomyopathy, Recessive (13 variants)
• Familial restrictive cardiomyopathy (13 variants)
• Hypertrophic cardiomyopathy (13 variants)
• DNAAF3-related condition (3 variants)
• Hypertrophic cardiomyopathy 7 (3 variants)
• Cardiomyopathy, familial restrictive, 1 (3 variants)
• Dilated cardiomyopathy 2A (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAAF3 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				82	1	83
missense	1	1	122	8	1	133
nonsense	6	1	2			9
start loss						0
frameshift	10	2	4			16
inframe indel	1		1			2
splice donor/acceptor (+/-2bp)	2	1	1			4
splice region	1		13	10		24
non coding	1	3	17	40	17	78
Total	21	8	147	130	19

Highest pathogenic variant AF is 0.000105

Variants in DNAAF3

This is a list of pathogenic ClinVar variants found in the DNAAF3 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-55159034-T-G		Primary ciliary dyskinesia	Uncertain significance (Jun 14, 2016)
19-55159062-T-C		Primary ciliary dyskinesia • Primary ciliary dyskinesia 2 • DNAAF3-related disorder	Uncertain significance (May 05, 2023)
19-55159083-T-C		Primary ciliary dyskinesia	Likely benign (Nov 13, 2023)
19-55159098-C-T		Primary ciliary dyskinesia	Likely benign (Sep 26, 2016)
19-55159099-G-A		Primary ciliary dyskinesia • Primary ciliary dyskinesia 2 • DNAAF3-related disorder	Conflicting classifications of pathogenicity (Aug 23, 2022)
19-55159102-GC-G		Primary ciliary dyskinesia 2 • Primary ciliary dyskinesia	Uncertain significance (Sep 27, 2019)
19-55159108-G-T		Primary ciliary dyskinesia	Uncertain significance (Jun 22, 2022)
19-55159110-C-T		Primary ciliary dyskinesia	Likely benign (Dec 13, 2022)
19-55159145-C-T		Primary ciliary dyskinesia	Uncertain significance (Jun 01, 2023)
19-55159152-C-T		Primary ciliary dyskinesia	Likely benign (Aug 23, 2016)
19-55159172-G-A		Primary ciliary dyskinesia	Uncertain significance (Aug 13, 2021)
19-55159179-G-A		Primary ciliary dyskinesia	Likely benign (May 06, 2022)
19-55159181-G-A		Primary ciliary dyskinesia	Uncertain significance (Aug 11, 2022)
19-55159193-C-T		Primary ciliary dyskinesia	Uncertain significance (Jan 29, 2021)
19-55159194-C-T		Primary ciliary dyskinesia	Likely benign (Jan 19, 2024)
19-55159197-C-T		Primary ciliary dyskinesia	Likely benign (Jul 06, 2019)
19-55159201-G-A		Primary ciliary dyskinesia	Uncertain significance (Aug 11, 2016)
19-55159201-G-T		Primary ciliary dyskinesia	Uncertain significance (Jul 03, 2022)
19-55159203-C-G		Primary ciliary dyskinesia	Uncertain significance (Dec 13, 2021)
19-55159212-G-GC		Primary ciliary dyskinesia	Uncertain significance (Jun 27, 2022)
19-55159216-TC-CT		Primary ciliary dyskinesia	Uncertain significance (Nov 10, 2018)
19-55159217-C-A		Primary ciliary dyskinesia	Uncertain significance (Aug 04, 2023)
19-55159235-C-T		Primary ciliary dyskinesia	Uncertain significance (Dec 09, 2023)
19-55159240-A-G		Primary ciliary dyskinesia	Likely benign (Jan 14, 2019)
19-55159245-C-G		Primary ciliary dyskinesia	Uncertain significance (Nov 15, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNAAF3	protein_coding	protein_coding	ENST00000527223	12	8060

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.54e-8	0.863	124741	0	86	124827	0.000345

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.412	318	339	0.937	0.0000191	3818
Missense in Polyphen		106	117.95	0.89866		1340
Synonymous	0.506	140	148	0.947	0.00000863	1324
Loss of Function	1.61	15	23.4	0.641	0.00000142	234

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000992	0.000983
Ashkenazi Jewish	0.0000997	0.0000993
East Asian	0.000337	0.000334
Finnish	0.0000949	0.0000928
European (Non-Finnish)	0.000348	0.000344
Middle Eastern	0.000337	0.000334
South Asian	0.000392	0.000392
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for the assembly of axonemal inner and outer dynein arms. Involved in preassembly of dyneins into complexes before their transport into cilia. {ECO:0000269|PubMed:22387996}.
• Disease: DISEASE: Ciliary dyskinesia, primary, 2 (CILD2) [MIM:606763]: A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. {ECO:0000269|PubMed:22387996}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• rvis_EVS: 0.67
• rvis_percentile_EVS: 84.61

Haploinsufficiency Scores

• pHI: 0.119
• hipred: N
• hipred_score: 0.236

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dnaaf3
• Phenotype: skeleton phenotype; respiratory system phenotype; liver/biliary system 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); growth/size/body region phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: dnaaf3
• Affected structure: ciliated cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: motile cilium assembly;axonemal dynein complex assembly
• Cellular component: cytoplasm