DNAH2

dynein axonemal heavy chain 2, the group of Dyneins, axonemal inner arm I1/f complex subunits

Basic information

Region (hg38): 17:7717743-7833742

Previous symbols: [ "DNHD3" ]

Links

ENSG00000183914 ∙ NCBI:146754 ∙ OMIM:603333 ∙ HGNC:2948 ∙ Uniprot:Q9P225 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spermatogenic failure 45 (Limited), mode of inheritance: AR
• spermatogenic failure 45 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spermatogenic failure 45	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Genitourinary	30811583

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNAH2 gene.

• Inborn genetic diseases (185 variants)
• not provided (50 variants)
• not specified (15 variants)
• Spermatogenic failure 45 (2 variants)
• - (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAH2 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				19	11	30
missense			185	17	11	213
nonsense	1					1
start loss						0
frameshift				1		1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	4	5
non coding					1	1
Total	1	0	185	37	23

Highest pathogenic variant AF is 0.00000658

Variants in DNAH2

This is a list of pathogenic ClinVar variants found in the DNAH2 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-7719726-G-T		DNAH2-related disorder	Likely benign (Mar 28, 2019)
17-7719796-G-C		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)
17-7719804-C-T		Inborn genetic diseases	Uncertain significance (Jan 23, 2023)
17-7719879-G-A		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
17-7719882-C-T		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
17-7719886-C-G		Inborn genetic diseases	Uncertain significance (Mar 07, 2024)
17-7727141-G-A		Inborn genetic diseases	Uncertain significance (Oct 29, 2021)
17-7727148-G-A		DNAH2-related disorder	Benign (Aug 28, 2019)
17-7727187-T-C		not specified • DNAH2-related disorder	Benign (Oct 21, 2019)
17-7733090-C-A		Inborn genetic diseases	Uncertain significance (Feb 23, 2023)
17-7733098-G-T		Inborn genetic diseases	Uncertain significance (Dec 11, 2023)
17-7733155-A-T		DNAH2-related disorder	Benign/Likely benign (Mar 01, 2023)
17-7733168-G-A		Inborn genetic diseases	Uncertain significance (Sep 07, 2022)
17-7733168-G-C		Inborn genetic diseases	Uncertain significance (Sep 13, 2023)
17-7733179-G-A		not specified • DNAH2-related disorder	Benign/Likely benign (Mar 25, 2019)
17-7733193-C-T		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
17-7733204-C-T		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
17-7733241-C-A		Inborn genetic diseases	Uncertain significance (Aug 10, 2023)
17-7733279-G-T		Inborn genetic diseases	Uncertain significance (Feb 22, 2023)
17-7733288-C-A		Inborn genetic diseases	Uncertain significance (May 31, 2023)
17-7734236-A-G		Inborn genetic diseases	Uncertain significance (Sep 26, 2023)
17-7734243-T-A		Inborn genetic diseases	Uncertain significance (Feb 14, 2024)
17-7734248-C-T		Inborn genetic diseases	Uncertain significance (Jan 08, 2024)
17-7734284-C-T		Primary microcephaly	Uncertain significance (Dec 01, 2020)
17-7734471-C-T		DNAH2-related disorder	Benign (Dec 18, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNAH2	protein_coding	protein_coding	ENST00000572933	85	116391

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.30e-44	1.00	124840	2	906	125748	0.00362

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.88	2317	2.59e+3	0.896	0.000164	29061
Missense in Polyphen		878	1037.6	0.84615		11963
Synonymous	-0.286	1022	1.01e+3	1.01	0.0000623	8628
Loss of Function	7.41	115	238	0.482	0.0000132	2584

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00437	0.00431
Ashkenazi Jewish	0.00527	0.00527
East Asian	0.000652	0.000653
Finnish	0.00390	0.00389
European (Non-Finnish)	0.00472	0.00469
Middle Eastern	0.000652	0.000653
South Asian	0.00318	0.00317
Other	0.00294	0.00294

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Force generating protein of respiratory cilia. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Involved in sperm motility; implicated in sperm flagellar assembly (By similarity). {ECO:0000250}.
• Pathway: Huntington,s disease - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.0978

Intolerance Scores

• loftool: 0.885
• rvis_EVS: -2.39
• rvis_percentile_EVS: 1.09

Haploinsufficiency Scores

• pHI: 0.104
• hipred: Y
• hipred_score: 0.576
• ghis: 0.440

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.150

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dnah2

Gene ontology

• Biological process: microtubule-based movement;cilium-dependent cell motility
• Cellular component: axonemal dynein complex;microtubule;dynein complex;motile cilium
• Molecular function: microtubule motor activity;ATP binding;ATP-dependent microtubule motor activity, minus-end-directed;dynein light chain binding;dynein intermediate chain binding;dynein light intermediate chain binding