U2AF2

U2 small nuclear RNA auxiliary factor 2, the group of RNA binding motif containing|Spliceosomal A complex|Spliceosomal E complex

Basic information

Region (hg38): 19:55654146-55674716

Links

ENSG00000063244 ∙ NCBI:11338 ∙ OMIM:191318 ∙ HGNC:23156 ∙ Uniprot:P26368 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental delay, dysmorphic facies, and brain anomalies (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental delay, dysmorphic facies, and brain anomalies	AD	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	Craniofacial; Dental; Neurologic	34112922; 36747105; 37092751; 37134193

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the U2AF2 gene.

• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the U2AF2 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				4	2	6
missense	1	5	26			32
nonsense						0
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding			1			1
Total	1	5	29	4	2

Variants in U2AF2

This is a list of pathogenic ClinVar variants found in the U2AF2 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-55655100-T-G			Uncertain significance (Jun 06, 2024)
19-55655118-A-C			Uncertain significance (Feb 15, 2023)
19-55655126-G-A		Inborn genetic diseases	Uncertain significance (May 23, 2024)
19-55659228-G-T			Uncertain significance (Sep 08, 2024)
19-55659254-T-C		Inborn genetic diseases	Uncertain significance (Oct 06, 2024)
19-55659270-G-A		Inborn genetic diseases	Uncertain significance (Mar 22, 2023)
19-55659270-G-T			Uncertain significance (Sep 11, 2024)
19-55659279-G-A		Inborn genetic diseases	Uncertain significance (Aug 02, 2022)
19-55659285-G-A			Uncertain significance (Sep 25, 2019)
19-55659293-G-A		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
19-55659342-G-A		Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
19-55659352-G-C		not specified	Uncertain significance (Nov 12, 2024)
19-55660513-CAGTCGTT-C			Uncertain significance (-)
19-55660517-C-T		Inborn genetic diseases	Uncertain significance (Aug 21, 2023)
19-55660527-G-A		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
19-55661071-C-T			Likely pathogenic (Sep 12, 2024)
19-55661087-C-A			Uncertain significance (Mar 03, 2024)
19-55661117-C-T		Inborn genetic diseases	Likely benign (Nov 24, 2024)
19-55661148-C-T		Inborn genetic diseases • Developmental delay, dysmorphic facies, and brain anomalies	Pathogenic/Likely pathogenic (May 17, 2024)
19-55661149-G-A			Uncertain significance (Apr 04, 2023)
19-55661151-C-T		Developmental delay, dysmorphic facies, and brain anomalies	Pathogenic/Likely pathogenic (Dec 15, 2024)
19-55661152-G-A		Inborn genetic diseases	Pathogenic (May 17, 2024)
19-55661159-C-T			Benign (Jul 13, 2018)
19-55661160-G-A			Pathogenic/Likely pathogenic (Jan 04, 2024)
19-55661162-G-T			Benign (Jul 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
U2AF2	protein_coding	protein_coding	ENST00000308924	12	20570

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000404	124915	0	32	124947	0.000128

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.71	83	320	0.259	0.0000218	3101
Missense in Polyphen		5	82.56	0.060562		831
Synonymous	-1.20	145	128	1.13	0.00000912	931
Loss of Function	4.39	0	22.4	0.00	0.00000109	251

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000243	0.000212
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000475	0.0000462
European (Non-Finnish)	0.000251	0.000232
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in pre-mRNA splicing and 3'-end processing (PubMed:17024186). By recruiting PRPF19 and the PRP19C/Prp19 complex/NTC/Nineteen complex to the RNA polymerase II C-terminal domain (CTD), and thereby pre-mRNA, may couple transcription to splicing (PubMed:21536736). Induces cardiac troponin-T (TNNT2) pre-mRNA exon inclusion in muscle. Regulates the TNNT2 exon 5 inclusion through competition with MBNL1. Binds preferentially to a single-stranded structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Required for the export of mRNA out of the nucleus, even if the mRNA is encoded by an intron-less gene. Represses the splicing of MAPT/Tau exon 10. Positively regulates pre-mRNA 3'-end processing by recruiting the CFIm complex to cleavage and polyadenylation signals (PubMed:17024186). {ECO:0000269|PubMed:15009664, ECO:0000269|PubMed:17024186, ECO:0000269|PubMed:19470458, ECO:0000269|PubMed:19574390, ECO:0000269|PubMed:21536736}.
• Pathway: Spliceosome - Homo sapiens (human);mRNA Processing;Gene expression (Transcription);spliceosomal assembly;RNA Polymerase II Transcription;Metabolism of RNA;Cleavage of Growing Transcript in the Termination Region ;RNA Polymerase II Transcription Termination;mRNA Splicing - Major Pathway;Transport of Mature mRNA derived from an Intron-Containing Transcript;mRNA Splicing;mRNA 3,-end processing;Transport of Mature Transcript to Cytoplasm;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.216
• rvis_EVS: -0.91
• rvis_percentile_EVS: 9.9

Haploinsufficiency Scores

• pHI: 0.426
• hipred: Y
• hipred_score: 0.831
• ghis: 0.704

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.962

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: U2af2

Gene ontology

• Biological process: mRNA splicing, via spliceosome;mRNA processing;RNA export from nucleus;mRNA export from nucleus;mRNA 3'-end processing;negative regulation of protein ubiquitination;positive regulation of RNA splicing;negative regulation of mRNA splicing, via spliceosome
• Cellular component: commitment complex;Prp19 complex;nucleus;nucleoplasm;spliceosomal complex;nuclear speck;U2-type prespliceosome;U2AF
• Molecular function: RNA binding;protein binding;poly-pyrimidine tract binding;enzyme binding;pre-mRNA 3'-splice site binding;C2H2 zinc finger domain binding