GeneBe

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

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Ullrich congenital muscular dystrophy 1B; Myosclerosis, autosomal recessive; Bethlem myopathy 1B; Epilepsy, progressive myoclonic, autosomal recessiveAD/ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingMusculoskeletal; Neurologic963533; 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 (1651 variants)
  • not_provided (841 variants)
  • Collagen_6-related_myopathy (179 variants)
  • not_specified (168 variants)
  • Inborn_genetic_diseases (167 variants)
  • Myosclerosis (125 variants)
  • COL6A2-related_disorder (124 variants)
  • Ullrich_congenital_muscular_dystrophy_1A (64 variants)
  • Ullrich_congenital_muscular_dystrophy_1B (36 variants)
  • Bethlem_myopathy_1B (26 variants)
  • Tip-toe_gait (6 variants)
  • BETHLEM_MYOPATHY_1B,_AUTOSOMAL_RECESSIVE (5 variants)
  • Abnormality_of_the_musculature (4 variants)
  • Myopathy (4 variants)
  • Bethlem_myopathy (3 variants)
  • See_cases (3 variants)
  • Glutamate_formiminotransferase_deficiency (3 variants)
  • Congenital_myopathy (2 variants)
  • Limb-girdle_muscular_dystrophy (2 variants)
  • Hip_flexor_weakness (1 variants)
  • Hyperextensible_hand_joints (1 variants)
  • Qualitative_or_quantitative_defects_of_collagen_6 (1 variants)
  • Charcot-Marie-Tooth_disease (1 variants)
  • Muscle_weakness (1 variants)
  • Limb-girdle_muscle_weakness (1 variants)
  • Proximal_muscle_weakness (1 variants)
  • Congenital_hip_dislocation (1 variants)
  • Fatigue (1 variants)
  • Congenital_muscular_dystrophy (1 variants)
  • Falls (1 variants)
  • Difficulty_walking (1 variants)
  • Muscular_dystrophy (1 variants)
  • COL6A2-related_core_myopathy (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. These statistics are base on transcript: NM_000001849.4. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
2
clinvar
26
clinvar
397
clinvar
11
clinvar
 437
missense
26
clinvar
61
clinvar
631
clinvar
194
clinvar
10
clinvar
 922
nonsense
25
clinvar
13
clinvar
 38
start loss
1
 1
frameshift
40
clinvar
26
clinvar
6
clinvar
 72
splice donor/acceptor (+/-2bp)
40
clinvar
43
clinvar
4
clinvar
1
clinvar
 88
Total 132 145 668 592 21

Highest pathogenic variant AF is 0.0000764335

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
COL6A2protein_codingprotein_codingENST00000300527 2734753
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
6.51e-81.001256830631257460.000251
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-1.157997131.120.00005496538
Missense in Polyphen320334.250.957362843
Synonymous-6.614633141.470.00002882069
Loss of Function4.062254.30.4050.00000284601

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0007060.000692
Ashkenazi Jewish0.0005010.000496
East Asian0.0001630.000163
Finnish0.000.00
European (Non-Finnish)0.0002620.000255
Middle Eastern0.0001630.000163
South Asian0.0002290.000229
Other0.0004910.000489

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

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

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