AFG2A

AFG2 AAA ATPase homolog A, the group of AAA ATPases

Basic information

Region (hg38): 4:122923070-123319433

Previous symbols: [ "SPATA5" ]

Links

ENSG00000145375 ∙ NCBI:166378 ∙ OMIM:613940 ∙ HGNC:18119 ∙ Uniprot:Q8NB90 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome (Strong), mode of inheritance: AR
• microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome (Definitive), mode of inheritance: AR
• microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome (Supportive), mode of inheritance: AR
• microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities	AR	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic	Although details are unclear, multiple individuals have been described as having immunodefiency, and awareness may allow prompt and aggressive treatment of infections; Among other findings, the condition can include sensorineural hearing loss, and some patients may benefit from early recognition and management of hearing loss	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Hematologic; Neurologic	21822266; 26299366

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AFG2A gene.

• Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome (44 variants)
• not provided (8 variants)
• Inborn genetic diseases (2 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AFG2A 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	141	3	147
missense	4	17	313	2	4	340
nonsense	22	6	1			29
start loss			2			2
frameshift	19	4				23
inframe indel		2	3			5
splice donor/acceptor (+/-2bp)	2	9				11
splice region			17	19	3	39
non coding		1	4	77	37	119
Total	47	39	326	220	44

Highest pathogenic variant AF is 0.000171

Variants in AFG2A

This is a list of pathogenic ClinVar variants found in the AFG2A region.

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

Position	Type	Phenotype	Significance	ClinVar
4-122923141-C-T			Uncertain significance (Apr 07, 2021)
4-122923143-A-C		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome • not specified	Conflicting classifications of pathogenicity (Mar 12, 2024)
4-122923143-A-G		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	Uncertain significance (Jul 05, 2022)
4-122923143-A-T		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	Uncertain significance (Aug 27, 2021)
4-122923144-T-C		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	Conflicting classifications of pathogenicity (Aug 23, 2022)
4-122923146-T-C		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	Uncertain significance (Aug 26, 2021)
4-122923151-CAAG-C		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	Uncertain significance (Jan 01, 2019)
4-122923152-A-T		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	Pathogenic (Dec 24, 2021)
4-122923155-A-G		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	Uncertain significance (Sep 13, 2022)
4-122923156-A-G			Uncertain significance (Jan 10, 2020)
4-122923157-G-A		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	Likely benign (May 31, 2022)
4-122923157-G-C		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	Uncertain significance (Jun 30, 2022)
4-122923158-A-G		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome • Inborn genetic diseases	Uncertain significance (Oct 13, 2022)
4-122923168-G-A		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	Uncertain significance (Apr 23, 2022)
4-122923170-T-C		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	Likely benign (Apr 23, 2021)
4-122923181-C-T		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	Likely benign (Jul 04, 2022)
4-122923187-A-C			Uncertain significance (Apr 04, 2019)
4-122923196-G-C		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	Likely benign (Jul 05, 2022)
4-122923199-C-T		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	Likely benign (May 03, 2022)
4-122923201-T-C		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	Uncertain significance (Mar 23, 2022)
4-122923203-C-T		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 22, 2023)
4-122923207-C-G		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	Uncertain significance (Apr 16, 2018)
4-122923213-C-G		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	Uncertain significance (Aug 27, 2021)
4-122923216-C-G		Inborn genetic diseases	Uncertain significance (Feb 28, 2024)
4-122923217-C-T		Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	Likely benign (Jan 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AFG2A	protein_coding	protein_coding	ENST00000274008	16	396377

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.08e-20	0.0558	125625	0	123	125748	0.000489

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.460	446	474	0.941	0.0000232	5803
Missense in Polyphen		151	182.91	0.82556		2171
Synonymous	0.601	163	173	0.942	0.00000844	1790
Loss of Function	1.14	34	42.0	0.810	0.00000250	504

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000606	0.000603
Ashkenazi Jewish	0.00	0.00
East Asian	0.000498	0.000489
Finnish	0.000278	0.000277
European (Non-Finnish)	0.000710	0.000703
Middle Eastern	0.000498	0.000489
South Asian	0.000328	0.000327
Other	0.000656	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: ATP-dependent chaperone which uses the energy provided by ATP hydrolysis to generate mechanical force to disassemble protein complexes. May be involved in morphological and functional mitochondrial transformations during spermatogenesis. {ECO:0000250|UniProtKB:P32794, ECO:0000250|UniProtKB:Q3UMC0}.
• Disease: DISEASE: Epilepsy, hearing loss, and mental retardation syndrome (EHLMRS) [MIM:616577]: An autosomal recessive disorder characterized by intellectual disability, intractable epilepsy, microcephaly, abnormal muscle tone, and sensorineural hearing loss. {ECO:0000269|PubMed:26299366}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Ribosome biogenesis in eukaryotes - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.181
• rvis_EVS: -0.22
• rvis_percentile_EVS: 37.66

Haploinsufficiency Scores

• pHI: 0.166
• hipred: N
• hipred_score: 0.204
• ghis: 0.564

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.385

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Spata5
• 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); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: spermatogenesis;brain development;cell differentiation
• Cellular component: cytoplasm;mitochondrion
• Molecular function: ATP binding;ATPase activity