EFTUD2

elongation factor Tu GTP binding domain containing 2, the group of Spliceosomal C complex|U5 small nuclear ribonucleoprotein|Spliceosomal Bact complex|Spliceosomal P complex

Basic information

Region (hg38): 17:44849947-44899445

Links

ENSG00000108883 ∙ NCBI:9343 ∙ OMIM:603892 ∙ HGNC:30858 ∙ Uniprot:Q15029 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mandibulofacial dysostosis-microcephaly syndrome (Definitive), mode of inheritance: AD
• mandibulofacial dysostosis-microcephaly syndrome (Strong), mode of inheritance: AD
• mandibulofacial dysostosis-microcephaly syndrome (Supportive), mode of inheritance: AD
• mandibulofacial dysostosis-microcephaly syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mandibulofacial dysostosis, Guion-Almeida type	AD	Audiologic/Otolaryngologic; Cardiovascular	Though the condition may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Recognition of potential GI manifestations (eg, Hirschsprung disease) may allow prompt treatment; The condition can involve congenital cardiac anomalies, and awareness may allow early management	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic	16760738; 19334086; 22541558; 22305528; 23188108; 25790162

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EFTUD2 gene.

• not provided (418 variants)
• Mandibulofacial dysostosis-microcephaly syndrome (71 variants)
• Inborn genetic diseases (29 variants)
• not specified (18 variants)
• EFTUD2-related condition (6 variants)
• See cases (4 variants)
• Global developmental delay (1 variants)
• Seizure;Global developmental delay (1 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EFTUD2 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			5	68	10	83
missense	5	13	118	10	3	149
nonsense	14	4				18
start loss						0
frameshift	26	9				35
inframe indel						0
splice donor/acceptor (+/-2bp)	16	13				29
splice region		3	17	14	5	39
non coding			4	63	79	146
Total	61	39	127	141	92

Variants in EFTUD2

This is a list of pathogenic ClinVar variants found in the EFTUD2 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-44851275-C-G			Likely pathogenic (Dec 22, 2021)
17-44851287-T-C		Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 28, 2023)
17-44851331-A-G			Benign (Jan 12, 2024)
17-44851334-G-A			Likely benign (Jul 18, 2023)
17-44851362-C-A		EFTUD2-related disorder	Uncertain significance (Nov 28, 2022)
17-44851381-G-C			Likely benign (Nov 04, 2022)
17-44851675-G-A			Benign (Jun 07, 2020)
17-44851692-G-A			Likely benign (Aug 21, 2022)
17-44851694-C-T			Likely benign (Nov 23, 2022)
17-44851698-A-G			Likely benign (Aug 27, 2022)
17-44851702-A-AGAT			Likely benign (Oct 17, 2022)
17-44851707-T-C			Uncertain significance (Jan 12, 2024)
17-44851708-AC-A		Mandibulofacial dysostosis-microcephaly syndrome	Pathogenic (Dec 01, 2012)
17-44851720-C-T			Pathogenic (Aug 02, 2023)
17-44851724-T-C			Uncertain significance (Jan 26, 2023)
17-44851728-G-A			Likely benign (Oct 05, 2023)
17-44851728-G-C			Uncertain significance (Mar 18, 2022)
17-44851728-G-T			Likely benign (Dec 05, 2023)
17-44851749-G-A			Likely benign (Nov 13, 2023)
17-44851763-G-A		Mandibulofacial dysostosis-microcephaly syndrome	Pathogenic (Feb 03, 2020)
17-44851777-C-CGGAT			Likely pathogenic (May 03, 2020)
17-44851802-G-A			Uncertain significance (Nov 10, 2022)
17-44851825-G-C			Likely benign (Nov 29, 2022)
17-44852051-G-A			Likely benign (Oct 27, 2018)
17-44852291-G-C			Benign (Jul 09, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EFTUD2	protein_coding	protein_coding	ENST00000426333	27	49720

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.08e-8	125713	0	1	125714	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.03	293	561	0.522	0.0000314	6417
Missense in Polyphen		75	243.93	0.30746		2766
Synonymous	0.545	212	222	0.954	0.0000135	1870
Loss of Function	6.45	1	50.4	0.0198	0.00000247	610

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the U5 snRNP and the U4/U6-U5 tri-snRNP complex required for pre-mRNA splicing. Binds GTP.
• Disease: DISEASE: Mandibulofacial dysostosis with microcephaly (MFDM) [MIM:610536]: A rare syndrome characterized by progressive microcephaly, midface and malar hypoplasia, micrognathia, microtia, dysplastic ears, preauricular skin tags, significant developmental delay, and speech delay. Many patients have major sequelae, including choanal atresia that results in respiratory difficulties, conductive hearing loss, and cleft palate. {ECO:0000269|PubMed:22305528}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Spliceosome - Homo sapiens (human);mRNA Processing;Metabolism of RNA;mRNA Splicing - Major Pathway;mRNA Splicing - Minor Pathway;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

• pRec: 0.337

Intolerance Scores

• loftool: 0.0218
• rvis_EVS: -1.15
• rvis_percentile_EVS: 6.23

Haploinsufficiency Scores

• pHI: 0.237
• hipred: Y
• hipred_score: 0.717
• ghis: 0.659

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.989

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Eftud2
• Phenotype: homeostasis/metabolism phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system 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)

Zebrafish Information Network

• Gene name: eftud2
• Affected structure: neuroblast (sensu Vertebrata)
• Phenotype tag: abnormal
• Phenotype quality: increased occurrence

Gene ontology

• Biological process: mRNA splicing, via spliceosome;mRNA processing;RNA splicing;cellular response to drug;response to cocaine
• Cellular component: nucleoplasm;spliceosomal complex;cytosol;Cajal body;membrane;nuclear speck;U4/U6 x U5 tri-snRNP complex;U2-type catalytic step 2 spliceosome;catalytic step 2 spliceosome;ribonucleoprotein complex
• Molecular function: RNA binding;GTPase activity;protein binding;GTP binding;U5 snRNA binding