COL5A2

collagen type V alpha 2 chain, the group of Collagens|MicroRNA protein coding host genes

Basic information

Region (hg38): 2:189031898-189225312

Links

ENSG00000204262 ∙ NCBI:1290 ∙ OMIM:120190 ∙ HGNC:2210 ∙ Uniprot:P05997 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 9.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_000393.5	NP_000384.2	54	yes	-
ENST00000374866.9	ENSP00000364000.3	54	yes	-
ENST00000618828.1	ENSP00000482184.1	40	-	-
ENST00000649966.1	ENSP00000496785.1	10	-	-

Phenotypes

GenCC

Source: genCC

• Ehlers-Danlos syndrome, classic type (Definitive), mode of inheritance: AD
• Ehlers-Danlos syndrome, classic type, 2 (Strong), mode of inheritance: AD
• Ehlers-Danlos syndrome, classic type, 2 (Strong), mode of inheritance: AD
• Ehlers-Danlos syndrome, classic type (Supportive), mode of inheritance: AD
• Ehlers-Danlos syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ehlers-Danlos syndrome, classic type, 2	AD	Cardiovascular; Obstetric	Individuals may have aortic root dilatation, but the natural history is unclear, and may not typically progress, though yearly surveillance with echocardiogram when aortic dilatation or mitral valve prolapse is peresent has been recommended; Precautions in pregnancy may be beneficial	Audiologic/Otolaryngologic; Cardiovascular; Dermatologic; Musculoskeletal; Obstetric; Ophthalmologic	9425231; 9783710; 12180144; 16278879; 15580559; 20301422; 20847697

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL5A2 gene.

• Ehlers-Danlos_syndrome,_classic_type,_1 (1674 variants)
• not_provided (592 variants)
• Familial_thoracic_aortic_aneurysm_and_aortic_dissection (520 variants)
• not_specified (292 variants)
• Ehlers-Danlos_syndrome,_classic_type,_2 (190 variants)
• COL5A2-related_disorder (62 variants)
• Ehlers-Danlos_syndrome (51 variants)
• Ehlers-Danlos_syndrome,_classic_type (47 variants)
• Connective_tissue_disorder (30 variants)
• Marfan_syndrome (4 variants)
• Cardiovascular_phenotype (3 variants)
• Abnormal_bleeding (2 variants)
• Telecanthus (2 variants)
• Thrombocytopenia (2 variants)
• Disproportionate_tall_stature (2 variants)
• Neuropathic_spinal_arthropathy (1 variants)
• Genetic_developmental_and_epileptic_encephalopathy (1 variants)
• Keratoconus (1 variants)
• Loeys-Dietz_syndrome (1 variants)
• Osteogenesis_imperfecta_type_III (1 variants)
• Familial_aortopathy (1 variants)
• See_cases (1 variants)
• Ehlers-Danlos_syndrome,_arthrochalasia_type (1 variants)
• Hyperextensible_skin (1 variants)
• Joint_hypermobility (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL5A2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000393.5. 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	2	18	427	8	456
missense	2	26	765	215	11	1019
nonsense	3		6			9
start loss			1			1
frameshift	7	2	5			14
splice donor/acceptor (+/-2bp)	8	15	21			44
Total	21	45	816	642	19

Highest pathogenic variant AF is 0.000047903446

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL5A2	protein_coding	protein_coding	ENST00000374866	54	147984

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125725	0	21	125746	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.44	679	883	0.769	0.0000484	9373
Missense in Polyphen		165	259.94	0.63475		2644
Synonymous	0.160	273	276	0.988	0.0000151	3279
Loss of Function	8.63	4	94.5	0.0423	0.00000513	1113

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000370	0.000370
European (Non-Finnish)	0.0000969	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Type V collagen is a member of group I collagen (fibrillar forming collagen). It is a minor connective tissue component of nearly ubiquitous distribution. Type V collagen binds to DNA, heparan sulfate, thrombospondin, heparin, and insulin. Type V collagen is a key determinant in the assembly of tissue- specific matrices (By similarity). {ECO:0000250}.
• Disease: DISEASE: Ehlers-Danlos syndrome, classic type, 2 (EDSCL2) [MIM:130010]: A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. The main features of classic Ehlers-Danlos syndrome are joint hypermobility and dislocation, and fragile, bruisable skin. EDSCL2 inheritance is autosomal dominant. {ECO:0000269|PubMed:27656288, ECO:0000269|PubMed:9425231, ECO:0000269|PubMed:9783710}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein digestion and absorption - Homo sapiens (human);miRNA targets in ECM and membrane receptors;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Collagen formation;Extracellular matrix organization;Integrin;Beta1 integrin cell surface interactions;Syndecan-1-mediated signaling events;Integrins in angiogenesis (Consensus)

Recessive Scores

• pRec: 0.391

Intolerance Scores

• loftool: 0.00489
• rvis_EVS: -0.87
• rvis_percentile_EVS: 10.59

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.331

Gene Damage Prediction

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

Gene ontology

• Biological process: skeletal system development;ossification;extracellular matrix organization;collagen fibril organization;notochord development;skin development;eye morphogenesis;cellular response to amino acid stimulus;negative regulation of endodermal cell differentiation
• Cellular component: extracellular region;collagen trimer;collagen type V trimer;extracellular space;endoplasmic reticulum lumen;extracellular matrix;collagen-containing extracellular matrix
• Molecular function: extracellular matrix structural constituent;extracellular matrix structural constituent conferring tensile strength;SMAD binding;metal ion binding