AFF2

ALF transcription elongation factor 2, the group of AF4/FMR2 family|Super elongation complex

Basic information

Region (hg38): X:148500617-149000663

Previous symbols: [ "FMR2" ]

Links

ENSG00000155966

∙ NCBI:2334 ∙ OMIM:300806 ∙ HGNC:3776 ∙ Uniprot:P51816 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

FRAXE intellectual disability (Strong), mode of inheritance: XL
FRAXE intellectual disability (Supportive), mode of inheritance: XL
FRAXE intellectual disability (Definitive), mode of inheritance: XL
non-syndromic X-linked intellectual disability (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Premature ovarian failure	XL	Obstetric	Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency	Endocrine; Neurologic; Obstetric	8334699; 8023854; 7536393; 7783162; 8673085; 8651274; 9341861; 9475603; 10528856; 12605436; 19136466; 21739600

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AFF2 gene.

not_provided (203 variants)
Inborn_genetic_diseases (106 variants)
FRAXE (50 variants)
not_specified (39 variants)
AFF2-related_disorder (21 variants)
Intellectual_disability (4 variants)
Non-syndromic_X-linked_intellectual_disability (3 variants)
Intellectual_disability,_moderate (1 variants)
Myopia (1 variants)
Hirsutism (1 variants)
Premature_ovarian_failure (1 variants)
Short_stature (1 variants)
Hypotonia (1 variants)
Primary_microcephaly (1 variants)
Synophrys (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AFF2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002025.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	36 clinvar	5 clinvar	46
missense	1 clinvar	4 clinvar	218 clinvar	45 clinvar	1 clinvar	269
nonsense	2 clinvar	2 clinvar				4
start loss						0
frameshift	2 clinvar	2 clinvar				4
splice donor/acceptor (+/-2bp)	1 clinvar	3 clinvar	3 clinvar			7
Total	6	11	226	81	6

Highest pathogenic variant AF is 0.000006638084

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AFF2	protein_coding	protein_coding	ENST00000370460	21	500055

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.996	0.00423	125735	4	8	125747	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.41	413	502	0.823	0.0000379	8652
Missense in Polyphen		183	237.35	0.77103		4184
Synonymous	-1.05	205	187	1.10	0.0000145	2582
Loss of Function	4.98	5	38.2	0.131	0.00000281	689

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000263	0.000234
Ashkenazi Jewish	0.00	0.00
East Asian	0.000145	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000505	0.0000352
Middle Eastern	0.000145	0.000109
South Asian	0.0000575	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: RNA-binding protein. Might be involved in alternative splicing regulation through an interaction with G-quartet RNA structure. {ECO:0000269|PubMed:19136466}.;

Recessive Scores

pRec: 0.280

Intolerance Scores

loftool: 0.205
rvis_EVS: -1.08
rvis_percentile_EVS: 7.2

Haploinsufficiency Scores

pHI: 0.317
hipred: Y
hipred_score: 0.580
ghis: 0.523

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.0786

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Aff2
Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); 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); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan);

Gene ontology

Biological process: regulation of transcription, DNA-templated;mRNA processing;brain development;learning or memory;RNA splicing;regulation of gene expression;negative regulation of gene expression;nuclear speck organization;regulation of RNA splicing
Cellular component: nucleus;transcription elongation factor complex;nuclear speck;ELL-EAF complex
Molecular function: G-quadruplex RNA binding;double-stranded DNA binding;DNA-binding transcription factor activity