EVC

EvC ciliary complex subunit 1

Basic information

Region (hg38): 4:5711201-5814305

Links

ENSG00000072840 ∙ NCBI:2121 ∙ OMIM:604831 ∙ HGNC:3497 ∙ Uniprot:P57679 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Ellis-van Creveld syndrome (Strong), mode of inheritance: AR
• acrofacial dysostosis, Weyers type (Limited), mode of inheritance: Unknown
• Ellis-van Creveld syndrome (Definitive), mode of inheritance: AR
• Ellis-van Creveld syndrome (Supportive), mode of inheritance: AR
• acrofacial dysostosis, Weyers type (Supportive), mode of inheritance: AD
• acrofacial dysostosis, Weyers type (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ellis-van Creveld syndrome	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Dental; Dermatologic; Musculoskeletal	7628126; 10700184; 17024374; 18454448; 18947413; 19744229; 20184732; 23220543

ClinVar

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

• Ellis-van_Creveld_syndrome (1590 variants)
• Curry-Hall_syndrome (1382 variants)
• not_provided (225 variants)
• Inborn_genetic_diseases (207 variants)
• not_specified (111 variants)
• EVC-related_disorder (56 variants)
• Short-rib_thoracic_dysplasia_6_with_or_without_polydactyly (4 variants)
• Nephronophthisis (1 variants)
• EVC-associated_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EVC gene is commonly pathogenic or not. These statistics are base on transcript: NM_000153717.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	20	551	4	576
missense	2	10	398	79	12	501
nonsense	53	30	1			84
start loss	2	4				6
frameshift	81	66	8			155
splice donor/acceptor (+/-2bp)	9	50	3			62
Total	147	161	430	630	16

Highest pathogenic variant AF is 0.0000532874

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EVC	protein_coding	protein_coding	ENST00000382674	21	117849

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125639	0	109	125748	0.000434

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.25	598	518	1.16	0.0000341	6398
Missense in Polyphen		157	130.02	1.2075		1653
Synonymous	-2.42	278	231	1.20	0.0000168	1979
Loss of Function	1.17	43	52.1	0.825	0.00000265	598

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000769	0.000767
Ashkenazi Jewish	0.00	0.00
East Asian	0.000382	0.000381
Finnish	0.000277	0.000277
European (Non-Finnish)	0.000513	0.000510
Middle Eastern	0.000382	0.000381
South Asian	0.000360	0.000359
Other	0.000820	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling. Involved in endochondral growth and skeletal development. {ECO:0000250|UniProtKB:P57680}.
• Disease: DISEASE: Acrofacial dysostosis, Weyers type (WAD) [MIM:193530]: An autosomal dominant condition characterized by dysplastic nails, postaxial polydactyly, dental anomalies, short limbs, short stature and normal intelligence. The phenotype is milder than Ellis-van Creveld syndrome. {ECO:0000269|PubMed:10700184}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Hedgehog signaling pathway - Homo sapiens (human);Hedgehog Signaling Pathway;Signal Transduction;Activation of SMO;Hedgehog ,on, state;Signaling by Hedgehog (Consensus)

Recessive Scores

• pRec: 0.180

Intolerance Scores

• loftool: 0.832
• rvis_EVS: 3.73
• rvis_percentile_EVS: 99.58

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.157

Gene Damage Prediction

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

Gene ontology

• Biological process: skeletal system development;endochondral bone growth;smoothened signaling pathway;muscle organ development;positive regulation of smoothened signaling pathway;cartilage development
• Cellular component: cytoplasm;cilium;integral component of membrane;ciliary basal body;ciliary membrane;plasma membrane protein complex