DNAAF2

dynein axonemal assembly factor 2, the group of Axonemal dynein assembly factors

Basic information

Region (hg38): 14:49625174-49635244

Previous symbols: [ "C14orf104" ]

Links

ENSG00000165506 ∙ ∙ OMIM:612517 ∙ HGNC:20188 ∙ Uniprot:Q9NVR5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary ciliary dyskinesia 10 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia 10 (Moderate), mode of inheritance: AR
• primary ciliary dyskinesia 10 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia (Supportive), mode of inheritance: AD
• primary ciliary dyskinesia 10 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary, 10	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	19052621; 20301301;

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNAAF2 gene.

• Primary ciliary dyskinesia (24 variants)
• Primary ciliary dyskinesia 10 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAAF2 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			5	140	5	150
missense			211	15	3	229
nonsense	9	4	2			15
start loss						0
frameshift	16	4	2			22
inframe indel			4			4
splice donor/acceptor (+/-2bp)						0
splice region			2	1		3
non coding			5	10	11	26
Total	25	8	229	165	19

Highest pathogenic variant AF is 0.00000657

Variants in DNAAF2

This is a list of pathogenic ClinVar variants found in the DNAAF2 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-49625214-T-A		Congenital disorder of glycosylation • Primary ciliary dyskinesia • Primary ciliary dyskinesia 10	Benign (Jan 12, 2018)
14-49625247-TAAAAC-T		Primary ciliary dyskinesia	Uncertain significance (Jun 14, 2016)
14-49625329-T-C		Primary ciliary dyskinesia 10	Uncertain significance (Jan 13, 2018)
14-49625351-T-C		Primary ciliary dyskinesia 10	Uncertain significance (Jan 13, 2018)
14-49625359-CA-C		Primary ciliary dyskinesia	Conflicting classifications of pathogenicity (Aug 15, 2019)
14-49625359-C-CA			Benign (Aug 10, 2019)
14-49625385-T-C		Primary ciliary dyskinesia 10	Uncertain significance (Jan 13, 2018)
14-49625416-A-T		Congenital disorder of glycosylation • Primary ciliary dyskinesia • Primary ciliary dyskinesia 10	Benign (Apr 10, 2019)
14-49625542-T-C		Primary ciliary dyskinesia	Likely benign (Oct 11, 2023)
14-49625551-A-G		Primary ciliary dyskinesia	Likely benign (Aug 02, 2019)
14-49625553-C-A		Primary ciliary dyskinesia	Uncertain significance (Sep 27, 2022)
14-49625557-T-C		Primary ciliary dyskinesia	Likely benign (Oct 20, 2023)
14-49625566-A-G		Primary ciliary dyskinesia	Likely benign (Jun 25, 2023)
14-49625566-AT-A		Primary ciliary dyskinesia	Uncertain significance (May 04, 2022)
14-49625581-T-C		Primary ciliary dyskinesia	Likely benign (Oct 22, 2019)
14-49625596-A-G		Primary ciliary dyskinesia • DNAAF2-related disorder	Likely benign (Jul 27, 2021)
14-49625607-T-C		Primary ciliary dyskinesia	Uncertain significance (Jan 10, 2019)
14-49625610-C-T		Primary ciliary dyskinesia	Uncertain significance (Aug 10, 2022)
14-49625616-C-A		Primary ciliary dyskinesia	Uncertain significance (Oct 24, 2018)
14-49625627-T-C		Primary ciliary dyskinesia	Uncertain significance (Feb 14, 2018)
14-49625628-G-A		Primary ciliary dyskinesia 10 • Primary ciliary dyskinesia	Conflicting classifications of pathogenicity (Jul 05, 2022)
14-49625630-A-C		Primary ciliary dyskinesia	Uncertain significance (Aug 11, 2022)
14-49625633-T-C		Primary ciliary dyskinesia	Uncertain significance (Nov 27, 2023)
14-49625635-G-C		Primary ciliary dyskinesia	Likely benign (Nov 24, 2019)
14-49625640-C-A		Primary ciliary dyskinesia	Uncertain significance (Jul 05, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNAAF2	protein_coding	protein_coding	ENST00000298292	3	10057

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.48e-9	0.672	125522	0	66	125588	0.000263

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.252	467	452	1.03	0.0000207	5324
Missense in Polyphen		156	148.6	1.0498		1743
Synonymous	-1.33	224	200	1.12	0.00000968	1753
Loss of Function	1.31	16	22.7	0.703	9.67e-7	307

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000975	0.000965
Ashkenazi Jewish	0.000103	0.0000993
East Asian	0.000337	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.000202	0.000194
Middle Eastern	0.000337	0.000326
South Asian	0.000264	0.000261
Other	0.000676	0.000653

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for cytoplasmic pre-assembly of axonemal dyneins, thereby playing a central role in motility in cilia and flagella. Involved in pre-assembly of dynein arm complexes in the cytoplasm before intraflagellar transport loads them for the ciliary compartment. {ECO:0000255|HAMAP-Rule:MF_03069}.
• Disease: DISEASE: Ciliary dyskinesia, primary, 10 (CILD10) [MIM:612518]: 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:19052621, ECO:0000269|PubMed:25186273}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Haploinsufficiency Scores

• pHI: 0.427
• hipred: N
• hipred_score: 0.204
• ghis: 0.458

Essentials

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

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dnaaf2
• 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); hematopoietic 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); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); digestive/alimentary phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: cilium-dependent cell motility;axonemal dynein complex assembly
• Cellular component: cytoplasm;cytosol
• Molecular function: protein binding