C2CD3

C2 domain containing 3 centriole elongation regulator, the group of C2 domain containing

Basic information

Region (hg38): 11:74012717-74171210

Links

ENSG00000168014 ∙ NCBI:26005 ∙ OMIM:615944 ∙ HGNC:24564 ∙ Uniprot:Q4AC94 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• orofaciodigital syndrome type 14 (Strong), mode of inheritance: AR
• orofaciodigital syndrome type 14 (Supportive), mode of inheritance: AR
• orofaciodigital syndrome type 14 (Strong), mode of inheritance: AR
• orofaciodigital syndrome type 14 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Craniofacial; Dental; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	AR	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	Cardiovascular; Craniofacial; Dental; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	24997988

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the C2CD3 gene.

• not provided (720 variants)
• Inborn genetic diseases (96 variants)
• Orofaciodigital syndrome type 14 (28 variants)
• not specified (9 variants)
• Familial aplasia of the vermis (3 variants)
• C2CD3-related condition (3 variants)
• Rudimentary fibula;Ankle flexion contracture (2 variants)
• Jeune thoracic dystrophy (2 variants)
• 7 conditions (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the C2CD3 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			7	117	20	144
missense	1	1	313	38	29	382
nonsense	5	2	2			9
start loss						0
frameshift	19	4	1			24
inframe indel			4		1	5
splice donor/acceptor (+/-2bp)	2	10	1			13
splice region			15	16	5	36
non coding			3	53	91	147
Total	27	17	331	208	141

Highest pathogenic variant AF is 0.0000328

Variants in C2CD3

This is a list of pathogenic ClinVar variants found in the C2CD3 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-74013403-C-T			Benign (Jan 25, 2024)
11-74013419-C-T			Likely benign (Dec 07, 2023)
11-74013420-G-A			Likely benign (Nov 24, 2023)
11-74013456-G-A			Uncertain significance (Jul 14, 2022)
11-74013460-G-A			Likely benign (Mar 09, 2022)
11-74013463-C-A			Benign/Likely benign (Jan 26, 2024)
11-74013467-T-C		C2CD3-related disorder	Benign/Likely benign (Jan 25, 2024)
11-74013479-C-T		Orofaciodigital syndrome type 14	Conflicting classifications of pathogenicity (Aug 02, 2022)
11-74013482-C-G			Likely benign (Dec 11, 2023)
11-74013496-G-A			Uncertain significance (Jan 15, 2024)
11-74013516-C-T			Uncertain significance (Oct 21, 2022)
11-74013540-G-A			Likely benign (Jun 28, 2022)
11-74013543-A-G			Likely benign (Nov 15, 2021)
11-74013545-C-G			Likely benign (Jan 15, 2024)
11-74028045-T-C			Benign (Jun 19, 2021)
11-74028245-T-G			Benign (May 11, 2021)
11-74028256-T-C			Benign (May 23, 2021)
11-74028288-T-G			Uncertain significance (Jul 26, 2022)
11-74028317-T-G			Likely benign (Aug 30, 2023)
11-74028323-G-A		C2CD3-related disorder	Likely benign (Jul 07, 2023)
11-74028375-T-C			Conflicting classifications of pathogenicity (Dec 22, 2023)
11-74028381-A-G			Uncertain significance (Aug 20, 2021)
11-74028389-G-A			Likely benign (Jul 17, 2023)
11-74028393-C-A			Uncertain significance (Sep 04, 2021)
11-74028608-C-G			Benign (May 11, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
C2CD3	protein_coding	protein_coding	ENST00000313663	31	158493

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.44e-19	1.00	125543	0	205	125748	0.000815

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.535	980	1.03e+3	0.953	0.0000521	12765
Missense in Polyphen		289	330.93	0.87329		4270
Synonymous	-0.0496	388	387	1.00	0.0000196	3937
Loss of Function	4.40	46	91.4	0.503	0.00000479	1092

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000931	0.000930
Ashkenazi Jewish	0.0000996	0.0000992
East Asian	0.000817	0.000816
Finnish	0.000788	0.000786
European (Non-Finnish)	0.00117	0.00116
Middle Eastern	0.000817	0.000816
South Asian	0.000402	0.000392
Other	0.000824	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the centrioles that acts as a positive regulator of centriole elongation (PubMed:24997988). Promotes assembly of centriolar distal appendage, a structure at the distal end of the mother centriole that acts as an anchor of the cilium, and is required for recruitment of centriolar distal appendages proteins CEP83, SCLT1, CEP89, FBF1 and CEP164. Not required for centriolar satellite integrity or RAB8 activation. Required for primary cilium formation (PubMed:23769972). Required for sonic hedgehog/SHH signaling and for proteolytic processing of GLI3. {ECO:0000269|PubMed:23769972, ECO:0000269|PubMed:24997988}.
• Disease: DISEASE: Orofaciodigital syndrome 14 (OFD14) [MIM:615948]: A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD14 patients show severe microcephaly, cerebral malformations the molar tooth sign, and intellectual disability in addition to canonical OFDS features. {ECO:0000269|PubMed:24997988}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Intolerance Scores

• loftool: 0.500
• rvis_EVS: 2.18
• rvis_percentile_EVS: 98.08

Haploinsufficiency Scores

• pHI: 0.371
• hipred: N
• hipred_score: 0.417
• ghis: 0.463

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: N
• gene_indispensability_score: 0.140

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: C2cd3
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); embryo phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype

Gene ontology

• Biological process: in utero embryonic development;heart looping;brain development;regulation of smoothened signaling pathway;protein processing;neural tube development;neural plate axis specification;regulation of proteolysis;embryonic digit morphogenesis;centriole elongation;protein localization to centrosome;ciliary basal body-plasma membrane docking;non-motile cilium assembly
• Cellular component: centrosome;centriole;cytosol;centriolar satellite;ciliary basal body
• Molecular function: protein binding