COL6A2

collagen type VI alpha 2 chain, the group of Collagens

Basic information

Region (hg38): 21:46098112-46132848

Links

ENSG00000142173 ∙ NCBI:1292 ∙ OMIM:120240 ∙ HGNC:2212 ∙ Uniprot:P12110 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bethlem myopathy 1A (Strong), mode of inheritance: AD
• Ullrich congenital muscular dystrophy 1A (Strong), mode of inheritance: AD
• Bethlem myopathy 1A (Strong), mode of inheritance: AR
• Ullrich congenital muscular dystrophy 1A (Strong), mode of inheritance: AR
• Bethlem myopathy (Supportive), mode of inheritance: AD
• Ullrich congenital muscular dystrophy (Supportive), mode of inheritance: AD
• myosclerosis (Supportive), mode of inheritance: AR
• Ullrich congenital muscular dystrophy 1A (Definitive), mode of inheritance: AR
• Ullrich congenital muscular dystrophy 1A (Definitive), mode of inheritance: AD
• Ullrich congenital muscular dystrophy 1A (Strong), mode of inheritance: AD
• Ullrich congenital muscular dystrophy 1A (Strong), mode of inheritance: AR
• collagen 6-related myopathy (Definitive), mode of inheritance: AD
• collagen 6-related myopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ullrich congenital muscular dystrophy 1B; Myosclerosis, autosomal recessive; Bethlem myopathy 1B; Epilepsy, progressive myoclonic, autosomal recessive	AD/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	Musculoskeletal; Neurologic	963533; 11381124; 12297580; 15563506; 15689448; 16075202; 15955946; 17886299; 18852439; 19564581; 20106987; 20302629; 20301676; 21280092; 23138527
Medical treatment (eg, with Cyclosporin A) may be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL6A2 gene.

• Bethlem myopathy 1A (92 variants)
• not provided (42 variants)
• Ullrich congenital muscular dystrophy 1A (4 variants)
• Inborn genetic diseases (2 variants)
• BETHLEM MYOPATHY 1B, AUTOSOMAL RECESSIVE (2 variants)
• Bethlem myopathy 1B (2 variants)
• Abnormality of the musculature (2 variants)
• Ullrich congenital muscular dystrophy 1B (1 variants)
• Bethlem myopathy (1 variants)
• Myosclerosis (1 variants)
• COL6A2-related disorder (1 variants)
• Bethlem myopathy 1A;Myosclerosis;Ullrich congenital muscular dystrophy 1A (1 variants)
• Bethlem myopathy 1A;Ullrich congenital muscular dystrophy 1A (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL6A2 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			16	258	12	286
missense	24	34	529	58	9	654
nonsense	23	5	1			29
start loss			1			1
frameshift	34	14	3			51
inframe indel			35			35
splice donor/acceptor (+/-2bp)	37	31	3	1	1	73
splice region	1	2	59	47	3	112
non coding	1		35	257	105	398
Total	119	84	623	574	127

Highest pathogenic variant AF is 0.0000722

Variants in COL6A2

This is a list of pathogenic ClinVar variants found in the COL6A2 region.

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

Position	Type	Phenotype	Significance	ClinVar
21-46098125-T-C		Collagen 6-related myopathy	Uncertain significance (Jan 12, 2018)
21-46098158-G-T		not specified	Likely benign (Mar 28, 2016)
21-46098272-T-C			Benign (Jul 03, 2018)
21-46111185-G-T			Benign (Jul 15, 2018)
21-46111207-C-A			Benign (Aug 03, 2018)
21-46111301-C-T			Benign (Jun 14, 2018)
21-46111342-G-C			Likely benign (Jun 16, 2018)
21-46111361-G-A			Benign (Jun 16, 2018)
21-46111447-C-G		Ullrich congenital muscular dystrophy 1A	Likely pathogenic (-)
21-46111471-G-A			Uncertain significance (Jan 25, 2016)
21-46111471-G-T		COL6A2-related disorder	Likely benign (Nov 06, 2023)
21-46111477-A-ATGCTCCAGGGCACC			Likely pathogenic (Mar 06, 2022)
21-46111479-G-A		Bethlem myopathy 1A	Uncertain significance (Dec 05, 2023)
21-46111481-T-C		Inborn genetic diseases	Uncertain significance (Mar 12, 2024)
21-46111488-C-T		Bethlem myopathy 1A	Uncertain significance (Aug 03, 2021)
21-46111490-C-T			Uncertain significance (Jan 26, 2016)
21-46111492-T-A		Myosclerosis • Bethlem myopathy 1A	Uncertain significance (Aug 11, 2022)
21-46111497-C-T		Bethlem myopathy 1A	Likely benign (Aug 22, 2021)
21-46111498-G-A		Bethlem myopathy 1A	Conflicting classifications of pathogenicity (Dec 22, 2023)
21-46111503-C-T		Bethlem myopathy 1A	Likely benign (Jun 14, 2023)
21-46111505-T-G		Bethlem myopathy 1A	Uncertain significance (Mar 27, 2023)
21-46111509-C-G		Bethlem myopathy 1A	Likely benign (Feb 04, 2022)
21-46111530-C-G		Collagen 6-related myopathy	Uncertain significance (Jan 13, 2018)
21-46111534-G-A		Bethlem myopathy 1A	Uncertain significance (Oct 02, 2019)
21-46111538-A-G		Bethlem myopathy 1A	Uncertain significance (Nov 22, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL6A2	protein_coding	protein_coding	ENST00000300527	27	34753

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.51e-8	1.00	125683	0	63	125746	0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.15	799	713	1.12	0.0000549	6538
Missense in Polyphen		320	334.25	0.95736		2843
Synonymous	-6.61	463	314	1.47	0.0000288	2069
Loss of Function	4.06	22	54.3	0.405	0.00000284	601

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000706	0.000692
Ashkenazi Jewish	0.000501	0.000496
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000262	0.000255
Middle Eastern	0.000163	0.000163
South Asian	0.000229	0.000229
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Collagen VI acts as a cell-binding protein.
• Disease: DISEASE: Bethlem myopathy 1 (BTHLM1) [MIM:158810]: A benign proximal myopathy characterized by early childhood onset and joint contractures most frequently affecting the elbows and ankles. {ECO:0000269|PubMed:11865138, ECO:0000269|PubMed:15689448, ECO:0000269|PubMed:17886299, ECO:0000269|PubMed:8782832}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ullrich congenital muscular dystrophy 1 (UCMD1) [MIM:254090]: A congenital myopathy characterized by muscle weakness and multiple joint contractures, generally noted at birth or early infancy. The clinical course is more severe than in Bethlem myopathy. {ECO:0000269|PubMed:15563506, ECO:0000269|PubMed:15689448}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myosclerosis autosomal recessive (MYOSAR) [MIM:255600]: A condition characterized by chronic inflammation of skeletal muscle with hyperplasia of the interstitial connective tissue. The clinical picture includes slender muscles with firm 'woody' consistency and restriction of movement of many joints because of muscle contractures. 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);miRNA targets in ECM and membrane receptors;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Developmental Biology;Assembly of collagen fibrils and other multimeric structures;Signal Transduction;Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Signaling by PDGF;Collagen formation;Extracellular matrix organization;Integrin;NCAM signaling for neurite out-growth;NCAM1 interactions;Axon guidance;Signaling by Receptor Tyrosine Kinases;Beta1 integrin cell surface interactions;Syndecan-1-mediated signaling events;Integrins in angiogenesis (Consensus)

Recessive Scores

• pRec: 0.379

Intolerance Scores

• loftool: 0.0126
• rvis_EVS: -1
• rvis_percentile_EVS: 8.22

Haploinsufficiency Scores

• pHI: 0.507
• hipred: Y
• hipred_score: 0.591
• ghis: 0.604

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.399

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Col6a2
• Phenotype: growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: col6a2
• Affected structure: muscle cell
• Phenotype tag: abnormal
• Phenotype quality: undifferentiated

Gene ontology

• Biological process: growth plate cartilage chondrocyte morphogenesis;cell adhesion;response to glucose;extracellular matrix organization;protein heterotrimerization
• Cellular component: extracellular region;collagen trimer;extracellular space;endoplasmic reticulum lumen;extracellular matrix;protein-containing complex;sarcolemma;collagen-containing extracellular matrix;extracellular exosome;extracellular vesicle
• Molecular function: protein binding;extracellular matrix structural constituent conferring tensile strength