EVC2

EvC ciliary complex subunit 2

Basic information

Region (hg38): 4:5542772-5709548

Links

ENSG00000173040 ∙ NCBI:132884 ∙ OMIM:607261 ∙ HGNC:19747 ∙ Uniprot:Q86UK5 ∙ 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 (Definitive), mode of inheritance: AR
• acrofacial dysostosis, Weyers type (Strong), mode of inheritance: AD
• Ellis-van Creveld syndrome (Supportive), mode of inheritance: AR
• acrofacial dysostosis, Weyers type (Supportive), mode of inheritance: AD
• Ellis-van Creveld syndrome (Definitive), mode of inheritance: AR
• Ellis-van Creveld syndrome (Strong), mode of inheritance: AR
• acrofacial dysostosis, Weyers type (Strong), mode of inheritance: AD

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	12468274; 12571802; 16404586; 17024374; 20184732; 21815252; 22406498; 23026208; 23220543; 23276573

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EVC2 gene.

• Curry-Hall syndrome;Ellis-van Creveld syndrome (76 variants)
• Ellis-van Creveld syndrome;Curry-Hall syndrome (73 variants)
• Ellis-van Creveld syndrome (17 variants)
• not provided (11 variants)
• not specified (2 variants)
• Short-rib thoracic dysplasia 6 with or without polydactyly (2 variants)
• Jeune thoracic dystrophy (2 variants)
• Inborn genetic diseases (2 variants)
• Curry-Hall syndrome (1 variants)
• Type IV short rib polydactyly syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EVC2 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	658	10	671
missense			379	19	13	411
nonsense	66	31	2			99
start loss			1			1
frameshift	82	49	4			135
inframe indel			15			15
splice donor/acceptor (+/-2bp)	7	54				61
splice region			12	104	2	118
non coding			9	267	98	374
Total	155	134	413	944	121

Highest pathogenic variant AF is 0.0000788

Variants in EVC2

This is a list of pathogenic ClinVar variants found in the EVC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-5562454-T-C		Ellis-van Creveld syndrome	Benign (Jan 13, 2018)
4-5562464-A-T		Ellis-van Creveld syndrome	Benign (Jan 13, 2018)
4-5562641-T-C		Ellis-van Creveld syndrome	Likely benign (Jan 12, 2018)
4-5562707-T-C		Ellis-van Creveld syndrome	Uncertain significance (Jan 13, 2018)
4-5562743-G-A		Ellis-van Creveld syndrome	Uncertain significance (Jan 13, 2018)
4-5562758-G-A		Ellis-van Creveld syndrome	Conflicting classifications of pathogenicity (Jun 10, 2021)
4-5562780-A-G		Ellis-van Creveld syndrome	Uncertain significance (Jan 13, 2018)
4-5562851-G-A		Ellis-van Creveld syndrome;Curry-Hall syndrome	Likely benign (May 09, 2023)
4-5562852-T-C		Inborn genetic diseases	Uncertain significance (Dec 08, 2023)
4-5562856-T-G		Ellis-van Creveld syndrome;Curry-Hall syndrome	Uncertain significance (Jun 27, 2022)
4-5562862-A-C		Ellis-van Creveld syndrome;Curry-Hall syndrome	Uncertain significance (Sep 30, 2022)
4-5562864-G-A		Ellis-van Creveld syndrome	Uncertain significance (Jan 13, 2018)
4-5562866-C-T		Ellis-van Creveld syndrome;Curry-Hall syndrome	Likely benign (Dec 07, 2022)
4-5562881-G-GGCATTCAAAAAGTTCTTCTTTTTC		Meckel-Gruber syndrome • not specified	Uncertain significance (Aug 08, 2024)
4-5562884-A-G		Ellis-van Creveld syndrome;Curry-Hall syndrome	Likely benign (Dec 20, 2023)
4-5562892-A-G		EVC2-related disorder	Uncertain significance (Jul 27, 2024)
4-5562893-G-A		Ellis-van Creveld syndrome;Curry-Hall syndrome	Likely benign (Jan 27, 2024)
4-5562893-GTTC-G		Ellis-van Creveld syndrome	Uncertain significance (May 24, 2023)
4-5562898-T-A			Uncertain significance (Dec 13, 2022)
4-5562905-C-T		Curry-Hall syndrome;Ellis-van Creveld syndrome	Likely benign (Dec 20, 2022)
4-5562907-T-G		Curry-Hall syndrome;Ellis-van Creveld syndrome	Likely benign (Oct 15, 2023)
4-5562908-G-A		Ellis-van Creveld syndrome;Curry-Hall syndrome	Likely benign (May 19, 2022)
4-5562911-A-T		Ellis-van Creveld syndrome;Curry-Hall syndrome	Likely benign (Jan 05, 2024)
4-5562911-AG-A		Ellis-van Creveld syndrome	Uncertain significance (Jan 31, 2018)
4-5562912-G-A			Uncertain significance (Nov 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EVC2	protein_coding	protein_coding	ENST00000344408	22	166777

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.02e-34	0.000605	125535	0	213	125748	0.000847

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.14	847	689	1.23	0.0000416	8474
Missense in Polyphen		210	184.8	1.1363		2551
Synonymous	-3.69	369	289	1.28	0.0000187	2580
Loss of Function	1.11	58	67.8	0.855	0.00000365	754

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00139	0.00138
Ashkenazi Jewish	0.00159	0.00159
East Asian	0.000925	0.000925
Finnish	0.00162	0.00162
European (Non-Finnish)	0.000743	0.000739
Middle Eastern	0.000925	0.000925
South Asian	0.000687	0.000686
Other	0.000984	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling. Plays a critical role in bone formation and skeletal development. May be involved in early embryonic morphogenesis. {ECO:0000250|UniProtKB:Q8K1G2}.
• 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:16404586}. 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: 0.134

Intolerance Scores

• loftool: 0.947
• rvis_EVS: -0.06
• rvis_percentile_EVS: 48.79

Haploinsufficiency Scores

• pHI: 0.117
• hipred: N
• hipred_score: 0.146
• ghis: 0.511

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.635

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Evc2
• Phenotype: cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; skeleton phenotype; limbs/digits/tail 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); normal phenotype

Gene ontology

• Biological process: smoothened signaling pathway
• Cellular component: nucleus;cytoplasm;cytoskeleton;cilium;integral component of membrane;ciliary membrane;plasma membrane protein complex