AFF2

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

Basic information

Region (hg38): X:148500616-149000663

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 (Definitive), mode of inheritance: XLR
• 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 (146 variants)
• Inborn genetic diseases (45 variants)
• FRAXE (39 variants)
• not specified (37 variants)
• Intellectual disability (3 variants)
• AFF2-related condition (2 variants)
• 7 conditions (1 variants)
• Premature ovarian failure (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.

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	24	5	32
missense		2	133	23	1	159
nonsense	2					2
start loss						0
frameshift	1					1
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)		2	2			4
splice region			9	1	1	11
non coding			7	5	3	15
Total	3	4	146	53	9

Variants in AFF2

This is a list of pathogenic ClinVar variants found in the AFF2 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-148500637-TGCCGCCGCCGCCGCCGCCGCCGCC-T			Likely benign (Feb 01, 2023)
X-148500637-TGCCGCCGCCGCCGCCGCCGCCGCCGCC-T		not specified	Uncertain significance (May 04, 2022)
X-148501124-C-T		Inborn genetic diseases	Likely benign (Oct 23, 2019)
X-148501128-G-A			Uncertain significance (Feb 28, 2023)
X-148501160-T-C		not specified	Likely benign (Jul 17, 2015)
X-148591261-G-C		FRAXE	Uncertain significance (Apr 23, 2021)
X-148652015-C-T			Uncertain significance (Mar 31, 2016)
X-148652027-A-T		Inborn genetic diseases	Pathogenic (Oct 13, 2016)
X-148652065-G-T		Inborn genetic diseases	Uncertain significance (Apr 28, 2022)
X-148652099-C-A			Uncertain significance (Jul 03, 2020)
X-148652115-A-G			Uncertain significance (Nov 23, 2022)
X-148652129-T-C			Uncertain significance (Aug 07, 2019)
X-148652130-A-G		Intellectual disability	Likely benign (Jan 01, 2019)
X-148661902-T-C			Uncertain significance (Jul 15, 2014)
X-148661926-C-T			Uncertain significance (Mar 08, 2016)
X-148661957-A-T			Uncertain significance (Sep 19, 2023)
X-148661960-A-G		Inborn genetic diseases	Uncertain significance (Jul 07, 2015)
X-148661961-T-C			Likely benign (May 01, 2023)
X-148661970-G-T			Uncertain significance (Jun 27, 2022)
X-148661978-T-C		Inborn genetic diseases	Uncertain significance (Jun 30, 2023)
X-148661983-A-C			Uncertain significance (Jun 01, 2020)
X-148661990-A-G		Inborn genetic diseases	Uncertain significance (May 28, 2020)
X-148662019-C-A		not specified	Uncertain significance (Sep 11, 2014)
X-148662021-A-G			Likely benign (Dec 31, 2019)
X-148662030-T-C		not specified • AFF2-related disorder	Benign (Apr 15, 2019)

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