EVC

EvC ciliary complex subunit 1

Basic information

Region (hg38): 4:5711200-5814305

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 (Definitive), mode of inheritance: AR
• acrofacial dysostosis, Weyers type (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 (Limited), mode of inheritance: Unknown
• Ellis-van Creveld syndrome (Strong), 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;Curry-Hall syndrome (596 variants)
• Ellis-van Creveld syndrome (491 variants)
• Curry-Hall syndrome;Ellis-van Creveld syndrome (384 variants)
• not provided (296 variants)
• not specified (72 variants)
• Inborn genetic diseases (62 variants)
• Curry-Hall syndrome (33 variants)
• EVC-related condition (12 variants)
• Short-rib thoracic dysplasia 6 with or without polydactyly (4 variants)
• EVC-Related Disorders (3 variants)
• Nephronophthisis (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.

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	378	12	393
missense		2	240	19	15	276
nonsense	39	17	1			57
start loss		4				4
frameshift	46	52	5			103
inframe indel		1	23			24
splice donor/acceptor (+/-2bp)	5	42				47
splice region	1	2	11	67	7	88
non coding		1	97	150	141	389
Total	90	119	369	547	168

Highest pathogenic variant AF is 0.000112

Variants in EVC

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

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

Position	Type	Phenotype	Significance	ClinVar
4-5711218-G-A		Ellis-van Creveld syndrome	Uncertain significance (Jan 12, 2018)
4-5711242-G-A		Ellis-van Creveld syndrome	Uncertain significance (Jan 13, 2018)
4-5711242-GGA-G		Ellis-van Creveld syndrome • Curry-Hall syndrome	Uncertain significance (Jun 14, 2016)
4-5711345-G-A		Ellis-van Creveld syndrome	Uncertain significance (Jan 12, 2018)
4-5711345-GC-AA		not specified	Likely benign (Feb 27, 2018)
4-5711346-C-A		Ellis-van Creveld syndrome	Uncertain significance (Jan 13, 2018)
4-5711351-TGCGGCGGGGCGGCAGCCTGAGCGCCCCGGATGGCCC-T		Curry-Hall syndrome;Ellis-van Creveld syndrome	Likely pathogenic (Sep 13, 2022)
4-5711361-C-A		Ellis-van Creveld syndrome	Uncertain significance (Jan 13, 2018)
4-5711380-GA-TT		Curry-Hall syndrome;Ellis-van Creveld syndrome	Pathogenic (Oct 25, 2022)
4-5711381-A-C		Curry-Hall syndrome;Ellis-van Creveld syndrome	Pathogenic (May 28, 2023)
4-5711381-A-G		Curry-Hall syndrome;Ellis-van Creveld syndrome	Likely pathogenic (Apr 09, 2022)
4-5711382-T-A		Ellis-van Creveld syndrome • Curry-Hall syndrome;Ellis-van Creveld syndrome	Pathogenic/Likely pathogenic (Dec 03, 2021)
4-5711382-T-C		Curry-Hall syndrome;Ellis-van Creveld syndrome	Likely pathogenic (Dec 31, 2021)
4-5711383-G-GTATAAGAGACA		Ellis-van Creveld syndrome	Likely pathogenic (Dec 17, 2021)
4-5711388-G-C		not specified • Ellis-van Creveld syndrome;Curry-Hall syndrome • Ellis-van Creveld syndrome • Inborn genetic diseases • EVC-related disorder	Conflicting classifications of pathogenicity (Mar 01, 2024)
4-5711389-C-A		Ellis-van Creveld syndrome;Curry-Hall syndrome	Likely benign (Jun 30, 2021)
4-5711388-G-GTGCTGCTGAGTGT		Ellis-van Creveld syndrome	Likely pathogenic (Mar 23, 2022)
4-5711392-CG-C		Ellis-van Creveld syndrome;Curry-Hall syndrome	Pathogenic (Sep 25, 2021)
4-5711394-G-T		Curry-Hall syndrome;Ellis-van Creveld syndrome	Likely benign (Dec 19, 2023)
4-5711393-G-GCTCA		Ellis-van Creveld syndrome	Likely pathogenic (Mar 18, 2022)
4-5711401-C-G		Ellis-van Creveld syndrome;Curry-Hall syndrome	Likely benign (Nov 06, 2023)
4-5711403-GC-G		Ellis-van Creveld syndrome • Curry-Hall syndrome;Ellis-van Creveld syndrome	Pathogenic/Likely pathogenic (Mar 31, 2023)
4-5711404-C-T		Ellis-van Creveld syndrome;Curry-Hall syndrome	Likely benign (Nov 09, 2023)
4-5711404-CA-C		Ellis-van Creveld syndrome	Likely pathogenic (Dec 30, 2021)
4-5711405-A-T		Ellis-van Creveld syndrome;Curry-Hall syndrome	Pathogenic (Nov 13, 2020)

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
3.46e-25	0.0133	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

Haploinsufficiency Scores

• pHI: 0.127
• hipred: N
• hipred_score: 0.270
• ghis: 0.434

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

Mouse Genome Informatics

• Gene name: Evc
• 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); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; limbs/digits/tail phenotype; craniofacial phenotype; growth/size/body region phenotype; cellular phenotype

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