DNAAF5

dynein axonemal assembly factor 5, the group of Axonemal dynein assembly factors|TOG domain containing

Basic information

Region (hg38): 7:726698-786475

Previous symbols: [ "HEATR2" ]

Links

ENSG00000164818 ∙ NCBI:54919 ∙ OMIM:614864 ∙ HGNC:26013 ∙ Uniprot:Q86Y56 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary ciliary dyskinesia 18 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia 18 (Moderate), mode of inheritance: AR
• primary ciliary dyskinesia 18 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia (Supportive), mode of inheritance: AD
• primary ciliary dyskinesia 18 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary, 18	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; Pulmonary	20350728; 23040496

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNAAF5 gene.

• Primary ciliary dyskinesia (509 variants)
• not provided (99 variants)
• Inborn genetic diseases (45 variants)
• Primary ciliary dyskinesia 18 (44 variants)
• not specified (31 variants)
• DNAAF5-related condition (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAAF5 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				166	11	177
missense		2	237	20	6	265
nonsense	8	1				9
start loss						0
frameshift	14	1	1			16
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	4	1			6
splice region			7	20	1	28
non coding				57	44	101
Total	23	8	240	243	61

Highest pathogenic variant AF is 0.0000460

Variants in DNAAF5

This is a list of pathogenic ClinVar variants found in the DNAAF5 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-726725-C-A		Primary ciliary dyskinesia	Uncertain significance (Nov 25, 2020)
7-726731-T-C		Primary ciliary dyskinesia	Conflicting classifications of pathogenicity (Jul 06, 2023)
7-726735-G-C		Primary ciliary dyskinesia	Likely benign (Feb 18, 2021)
7-726737-T-C		Primary ciliary dyskinesia	Uncertain significance (Jun 15, 2022)
7-726739-G-A		Primary ciliary dyskinesia	Uncertain significance (Sep 26, 2023)
7-726742-G-C		Primary ciliary dyskinesia	Uncertain significance (Jul 21, 2022)
7-726743-A-C		Primary ciliary dyskinesia	Uncertain significance (Aug 26, 2022)
7-726744-G-A		Primary ciliary dyskinesia • DNAAF5-related disorder	Likely benign (Dec 13, 2023)
7-726747-C-T		Primary ciliary dyskinesia	Likely benign (Nov 18, 2023)
7-726748-G-C		Primary ciliary dyskinesia	Uncertain significance (Aug 26, 2021)
7-726750-G-A		Primary ciliary dyskinesia	Likely benign (Apr 30, 2023)
7-726755-C-A		Primary ciliary dyskinesia	Uncertain significance (Mar 26, 2023)
7-726769-G-A		Primary ciliary dyskinesia	Uncertain significance (Jan 04, 2024)
7-726770-A-AG		Primary ciliary dyskinesia 18	Pathogenic (Sep 12, 2019)
7-726771-G-A		Primary ciliary dyskinesia	Likely benign (Dec 03, 2023)
7-726775-G-T		Primary ciliary dyskinesia	Uncertain significance (Apr 02, 2021)
7-726783-G-C		Primary ciliary dyskinesia	Likely benign (Mar 04, 2023)
7-726785-C-T		Primary ciliary dyskinesia	Uncertain significance (Jan 16, 2024)
7-726787-G-C		Primary ciliary dyskinesia	Uncertain significance (Jul 19, 2022)
7-726789-G-A		Primary ciliary dyskinesia	Likely benign (Jun 04, 2022)
7-726789-G-T		Primary ciliary dyskinesia	Uncertain significance (Jan 18, 2024)
7-726792-G-A		not specified • Primary ciliary dyskinesia	Benign (Jan 31, 2024)
7-726798-G-A		Primary ciliary dyskinesia	Likely benign (Jul 27, 2021)
7-726799-C-G		Primary ciliary dyskinesia	Uncertain significance (Sep 15, 2021)
7-726801-G-A		Primary ciliary dyskinesia	Likely benign (Mar 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNAAF5	protein_coding	protein_coding	ENST00000297440	13	62853

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.10e-11	0.883	125697	0	51	125748	0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.00234	440	440	1.00	0.0000297	5353
Missense in Polyphen		110	118.99	0.92448		1411
Synonymous	-1.37	239	214	1.12	0.0000164	1905
Loss of Function	1.85	21	32.3	0.649	0.00000191	340

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000749	0.000747
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000195	0.000167
Middle Eastern	0.000163	0.000163
South Asian	0.000263	0.000261
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cytoplasmic protein involved in the delivery of the dynein machinery to the motile cilium. It is required for the assembly of the axonemal dynein inner and outer arms, two structures attached to the peripheral outer doublet A microtubule of the axoneme, that play a crucial role in cilium motility. {ECO:0000269|PubMed:23040496, ECO:0000269|PubMed:25232951}.
• Disease: DISEASE: Ciliary dyskinesia, primary, 18 (CILD18) [MIM:614874]: 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:23040496, ECO:0000269|PubMed:25232951}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.101

Intolerance Scores

• rvis_EVS: -0.57
• rvis_percentile_EVS: 19.04

Haploinsufficiency Scores

• pHI: 0.155
• hipred: N
• hipred_score: 0.229
• ghis: 0.622

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Dnaaf5

Gene ontology

• Biological process: cilium movement;outer dynein arm assembly;inner dynein arm assembly
• Cellular component: cytoplasm;motile cilium
• Molecular function: dynein intermediate chain binding