COL9A2

collagen type IX alpha 2 chain, the group of Collagen proteoglycans|Collagens

Basic information

Region (hg38): 1:40300488-40317813

Previous symbols: [ "EDM2" ]

Links

ENSG00000049089 ∙ NCBI:1298 ∙ OMIM:120260 ∙ HGNC:2218 ∙ Uniprot:Q14055 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Stickler syndrome, type 5 (Strong), mode of inheritance: AR
• Stickler syndrome, type 5 (Definitive), mode of inheritance: AR
• epiphyseal dysplasia, multiple, 2 (Definitive), mode of inheritance: AD
• Stickler syndrome, type 5 (Strong), mode of inheritance: AR
• multiple epiphyseal dysplasia due to collagen 9 anomaly (Supportive), mode of inheritance: AD
• autosomal recessive Stickler syndrome (Supportive), mode of inheritance: AR
• epiphyseal dysplasia, multiple, 2 (Strong), mode of inheritance: AD
• Stickler syndrome, type 5 (Strong), mode of inheritance: AR
• Stickler syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Stickler syndrome, Type V	AR	Audiologic/Otolaryngologic; Ophthalmologic	Though the condition may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Avoidance of risk factors related to ocular manifestations (eg, contact sports) is indicated	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Ophthalmologic	3238439; 8528240; 12244547; 15633184; 20358595; 21671392; 20301479

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL9A2 gene.

• not provided (801 variants)
• Epiphyseal dysplasia, multiple, 2 (99 variants)
• not specified (77 variants)
• Inborn genetic diseases (32 variants)
• Connective tissue disorder (21 variants)
• COL9A2-related condition (9 variants)
• Epiphyseal dysplasia, multiple, 2;Stickler syndrome, type 5 (8 variants)
• Stickler syndrome, type 5;Epiphyseal dysplasia, multiple, 2 (4 variants)
• Stickler syndrome, type 5 (4 variants)
• See cases (2 variants)
• Stickler syndrome (2 variants)
• COL9A2-Related Disorders (1 variants)
• Intellectual disability (1 variants)
• Intervertebral disc disease, susceptibility to (1 variants)
• Intervertebral disc disorder;Stickler syndrome, type 5;Epiphyseal dysplasia, multiple, 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL9A2 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			8	108	3	119
missense		1	293	12	8	314
nonsense	4	3	4	1		12
start loss						0
frameshift	11	5	3			19
inframe indel			7			7
splice donor/acceptor (+/-2bp)	1	3	13			17
splice region	1	1	26	38	7	73
non coding			19	176	60	255
Total	16	12	347	297	71

Highest pathogenic variant AF is 0.00000659

Variants in COL9A2

This is a list of pathogenic ClinVar variants found in the COL9A2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-40300499-C-T		Epiphyseal dysplasia, multiple, 2	Uncertain significance (Jan 13, 2018)
1-40300604-G-A		Epiphyseal dysplasia, multiple, 2	Benign (Jan 13, 2018)
1-40300621-T-C		Epiphyseal dysplasia, multiple, 2	Likely benign (Jan 13, 2018)
1-40300639-C-T		Epiphyseal dysplasia, multiple, 2	Benign (Jan 12, 2018)
1-40300739-G-A		Epiphyseal dysplasia, multiple, 2	Uncertain significance (Jan 13, 2018)
1-40300777-C-T		Epiphyseal dysplasia, multiple, 2	Uncertain significance (Jan 13, 2018)
1-40300796-G-A		Epiphyseal dysplasia, multiple, 2	Uncertain significance (Jan 12, 2018)
1-40300812-C-T		Epiphyseal dysplasia, multiple, 2	Uncertain significance (Jan 12, 2018)
1-40300813-G-A		Epiphyseal dysplasia, multiple, 2	Uncertain significance (Jan 12, 2018)
1-40300860-C-T		Epiphyseal dysplasia, multiple, 2	Uncertain significance (Jan 13, 2018)
1-40300870-A-T		Epiphyseal dysplasia, multiple, 2	Benign (Jan 13, 2018)
1-40300919-G-A		Epiphyseal dysplasia, multiple, 2	Benign (Jan 12, 2018)
1-40300946-C-T		Epiphyseal dysplasia, multiple, 2	Benign (Jun 26, 2018)
1-40300952-G-A		Epiphyseal dysplasia, multiple, 2	Uncertain significance (Jan 13, 2018)
1-40301060-A-G		Epiphyseal dysplasia, multiple, 2	Benign (Jun 26, 2018)
1-40301071-G-A		Epiphyseal dysplasia, multiple, 2	Benign (Jan 12, 2018)
1-40301115-T-C		Epiphyseal dysplasia, multiple, 2	Uncertain significance (Jan 13, 2018)
1-40301144-C-T		Epiphyseal dysplasia, multiple, 2	Uncertain significance (Jan 12, 2018)
1-40301183-C-T			Likely benign (Jul 05, 2022)
1-40301189-C-T			Uncertain significance (Jan 13, 2023)
1-40301191-C-G			Uncertain significance (Sep 02, 2022)
1-40301193-T-C		Stickler syndrome, type 5;Epiphyseal dysplasia, multiple, 2;Intervertebral disc disorder • Epiphyseal dysplasia, multiple, 2	Conflicting classifications of pathogenicity (Jan 29, 2024)
1-40301194-G-A		Epiphyseal dysplasia, multiple, 2	Conflicting classifications of pathogenicity (Jan 28, 2024)
1-40301196-T-C			Uncertain significance (Jul 19, 2022)
1-40301201-C-T			Uncertain significance (Feb 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL9A2	protein_coding	protein_coding	ENST00000372748	32	17330

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.05e-8	1.00	118207	316	7225	125748	0.0304

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.34	354	432	0.819	0.0000261	4182
Missense in Polyphen		114	157.99	0.72158		1447
Synonymous	0.934	153	168	0.908	0.0000113	1514
Loss of Function	3.61	22	49.4	0.445	0.00000265	541

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.175	0.174
Ashkenazi Jewish	0.00119	0.00119
East Asian	0.113	0.113
Finnish	0.0116	0.0116
European (Non-Finnish)	0.00239	0.00238
Middle Eastern	0.113	0.113
South Asian	0.0334	0.0333
Other	0.0193	0.0191

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Structural component of hyaline cartilage and vitreous of the eye.
• Disease: DISEASE: Multiple epiphyseal dysplasia 2 (EDM2) [MIM:600204]: A generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. Radiological examination of the skeleton shows delayed, irregular mineralization of the epiphyseal ossification centers and of the centers of the carpal and tarsal bones. Multiple epiphyseal dysplasia is broadly categorized into the more severe Fairbank and the milder Ribbing types. The Fairbank type is characterized by shortness of stature, short and stubby fingers, small epiphyses in several joints, including the knee, ankle, hand, and hip. The Ribbing type is confined predominantly to the hip joints and is characterized by hands that are normal and stature that is normal or near-normal. {ECO:0000269|PubMed:10364514}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Intervertebral disc disease (IDD) [MIM:603932]: A common musculo-skeletal disorder caused by degeneration of intervertebral disks of the lumbar spine. It results in low-back pain and unilateral leg pain. {ECO:0000269|PubMed:10411504}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Stickler syndrome 5 (STL5) [MIM:614284]: An autosomal recessive form of Stickler syndrome, an inherited disorder that associates ocular signs with more or less complete forms of Pierre Robin sequence, bone disorders and sensorineural deafness. STL5 is characterized by high myopia, vitreoretinal degeneration, retinal detachment, mild to moderate sensorineural hearing loss, short stature in childhood, and absence of cleft palate and Pierre Robin sequence. {ECO:0000269|PubMed:21671392}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Protein digestion and absorption - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);PI3K-Akt Signaling Pathway;Developmental Biology;Assembly of collagen fibrils and other multimeric structures;Signal Transduction;Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Integrin cell surface interactions;Collagen degradation;Signaling by PDGF;Collagen formation;Extracellular matrix organization;Integrin;Degradation of the extracellular matrix;NCAM signaling for neurite out-growth;NCAM1 interactions;Axon guidance;ECM proteoglycans;Signaling by Receptor Tyrosine Kinases (Consensus)

Recessive Scores

• pRec: 0.163

Intolerance Scores

• loftool: 0.0969
• rvis_EVS: 1.69
• rvis_percentile_EVS: 96.41

Haploinsufficiency Scores

• pHI: 0.110
• hipred: N
• hipred_score: 0.475
• ghis: 0.378

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.636

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Col9a2
• Phenotype: hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; skeleton phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: skeletal system development;extracellular matrix organization
• Cellular component: extracellular region;collagen type IX trimer;basement membrane;extracellular space;endoplasmic reticulum lumen;extracellular matrix
• Molecular function: extracellular matrix structural constituent;extracellular matrix structural constituent conferring tensile strength