DNAAF1

dynein axonemal assembly factor 1, the group of Axonemal dynein assembly factors

Basic information

Region (hg38): 16:84145287-84178767

Previous symbols: [ "LRRC50" ]

Links

ENSG00000154099 ∙ NCBI:123872 ∙ OMIM:613190 ∙ HGNC:30539 ∙ Uniprot:Q8NEP3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary ciliary dyskinesia 13 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia (Supportive), mode of inheritance: AD
• primary ciliary dyskinesia 13 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia 13 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary, 13	AR	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; 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, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary	19944405; 19944400; 20301301

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNAAF1 gene.

• Primary ciliary dyskinesia (31 variants)
• Primary ciliary dyskinesia 13 (6 variants)
• not provided (1 variants)
• Kartagener syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAAF1 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			3	94	5	102
missense		1	233	16	11	261
nonsense	14	1				15
start loss						0
frameshift	18	2	2			22
inframe indel			6			6
splice donor/acceptor (+/-2bp)	1	2	1			4
splice region			7	10	1	18
non coding			7	42	56	105
Total	33	6	252	152	72

Highest pathogenic variant AF is 0.0000330

Variants in DNAAF1

This is a list of pathogenic ClinVar variants found in the DNAAF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-84145295-G-C		Primary ciliary dyskinesia	Uncertain significance (Jun 14, 2016)
16-84145300-G-A		Primary ciliary dyskinesia	Uncertain significance (Jun 14, 2016)
16-84145313-G-C		Primary ciliary dyskinesia 13	Uncertain significance (Jan 13, 2018)
16-84145341-G-A		Primary ciliary dyskinesia 13	Uncertain significance (Jan 13, 2018)
16-84145357-C-CT		Primary ciliary dyskinesia	Likely benign (Jun 14, 2016)
16-84145375-T-C		Primary ciliary dyskinesia 13	Benign (Apr 27, 2017)
16-84145422-C-T		not specified	Likely benign (-)
16-84145443-G-A			Uncertain significance (Sep 16, 2018)
16-84145444-C-A		Primary ciliary dyskinesia	Uncertain significance (Aug 26, 2021)
16-84145447-C-T		Primary ciliary dyskinesia	Uncertain significance (Nov 09, 2021)
16-84145453-C-G		Primary ciliary dyskinesia	Conflicting classifications of pathogenicity (Aug 14, 2023)
16-84145457-C-T		Primary ciliary dyskinesia	Uncertain significance (Dec 03, 2024)
16-84145469-C-T		Primary ciliary dyskinesia	Uncertain significance (Dec 27, 2022)
16-84145469-CA-C		Primary ciliary dyskinesia	Pathogenic (Dec 24, 2021)
16-84145472-G-C		Primary ciliary dyskinesia	Uncertain significance (Mar 10, 2021)
16-84145473-T-C		Primary ciliary dyskinesia	Likely benign (May 24, 2022)
16-84145479-A-C		Primary ciliary dyskinesia	Likely benign (Jul 27, 2023)
16-84145486-C-G		Primary ciliary dyskinesia	Uncertain significance (Jul 12, 2022)
16-84145489-G-T		Primary ciliary dyskinesia	Uncertain significance (Apr 23, 2024)
16-84145498-C-T		Primary ciliary dyskinesia	Pathogenic (Feb 21, 2022)
16-84145499-A-G		Primary ciliary dyskinesia	Uncertain significance (Aug 27, 2024)
16-84145505-C-T		Primary ciliary dyskinesia 13	Uncertain significance (Jan 12, 2018)
16-84145508-G-A		Primary ciliary dyskinesia	Uncertain significance (Feb 15, 2023)
16-84145513-G-C		Primary ciliary dyskinesia	Uncertain significance (Jan 26, 2019)
16-84145516-G-C		Primary ciliary dyskinesia	Uncertain significance (Oct 04, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNAAF1	protein_coding	protein_coding	ENST00000378553	12	33509

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.47e-12	0.680	125530	0	218	125748	0.000867

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.99	502	391	1.28	0.0000224	4702
Missense in Polyphen		85	74.164	1.1461		987
Synonymous	-1.74	191	163	1.17	0.0000106	1435
Loss of Function	1.56	22	31.4	0.700	0.00000163	390

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00251	0.00251
Ashkenazi Jewish	0.00218	0.00218
East Asian	0.000326	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.000757	0.000756
Middle Eastern	0.000326	0.000326
South Asian	0.000523	0.000523
Other	0.00147	0.00147

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cilium-specific protein required for the stability of the ciliary architecture. Plays a role in cytoplasmic preassembly of dynein arms. Involved in regulation of microtubule-based cilia and actin-based brush border microvilli. {ECO:0000269|PubMed:18385425, ECO:0000269|PubMed:19944400, ECO:0000269|PubMed:19944405}.

Recessive Scores

• pRec: 0.0657

Intolerance Scores

• rvis_EVS: 2.75
• rvis_percentile_EVS: 98.97

Haploinsufficiency Scores

• pHI: 0.0606
• hipred: N
• hipred_score: 0.145

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: Dnaaf1
• 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); craniofacial phenotype; 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); skeleton phenotype

Zebrafish Information Network

• Gene name: dnaaf1
• Affected structure: spermatogonium
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: heart looping;cilium movement;regulation of cilium beat frequency;lung development;determination of pancreatic left/right asymmetry;outer dynein arm assembly;inner dynein arm assembly;motile cilium assembly;cilium assembly;epithelial cilium movement involved in determination of left/right asymmetry;left/right pattern formation;axonemal dynein complex assembly;determination of digestive tract left/right asymmetry;determination of liver left/right asymmetry
• Cellular component: spindle pole;cytoplasm;cytosol;plasma membrane;axoneme;nuclear speck
• Molecular function: dynein complex binding