Type 2 collagenopathy: genes and variants

Genes linked to Type 2 collagenopathy

• COL2A1: Collagen alpha-1(II) chain

  It provides the principal fibrillar collagen framework of cartilage and is also important in the vitreous and inner ear. Pathogenic variants cause a broad type II collagenopathy spectrum including Stickler syndrome, spondyloepiphyseal dysplasia, and severe skeletal dysplasias.

  14 disease-causing and 32 uncertain variants in COL2A1 are linked to Type 2 collagenopathy.

Known disease-causing variants in Type 2 collagenopathy

Which prediction tools work for Type 2 collagenopathy

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 94 out of 100

Same protein, different disease

• Spondyloepiphyseal dysplasia congenita is also caused by COL2A1 variants; they fall mostly in different places as the Type 2 collagenopathy variants (38 disease-causing).
• Achondrogenesis type II is also caused by COL2A1 variants; they fall mostly in different places as the Type 2 collagenopathy variants (34 disease-causing).
• Stickler syndrome is also caused by COL2A1 variants; they fall mostly in different places as the Type 2 collagenopathy variants (26 disease-causing).
• Spondyloepimetaphyseal dysplasia, Strudwick type is also caused by COL2A1 variants; they fall mostly in different places as the Type 2 collagenopathy variants (18 disease-causing).
• Connective tissue disorder is also caused by COL2A1 variants; they fall mostly in different places as the Type 2 collagenopathy variants (15 disease-causing).

Diseases related to Type 2 collagenopathy

• Spondyloepiphyseal dysplasia congenita, also linked to COL2A1
• Achondrogenesis type II, also linked to COL2A1
• Stickler syndrome, also linked to COL2A1
• Connective tissue disorder, also linked to COL2A1
• Spondyloepimetaphyseal dysplasia, Strudwick type, also linked to COL2A1
• Spondyloperipheral dysplasia, also linked to COL2A1
• Fetal anomalies with a likely genetic cause, also linked to COL2A1
• Spondyloepiphyseal dysplasia, Stanescu type, also linked to COL2A1
• Platyspondylic dysplasia, Torrance type, also linked to COL2A1
• Kniest dysplasia, also linked to COL2A1
• Stickler syndrome, type I, nonsyndromic ocular, also linked to COL2A1
• Paediatric disorders, also linked to COL2A1

Frequently asked questions

Which genes are linked to Type 2 collagenopathy?

In CATVariant, Type 2 collagenopathy is linked to 1 analyzed protein: COL2A1 (Collagen alpha-1(II) chain).

How many genetic variants are linked to Type 2 collagenopathy?

54 variants: 14 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 32 are of uncertain significance or have conflicting reports.

Which uncertain variants in Type 2 collagenopathy look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Type 2 collagenopathy?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.94, based on 11 disease-causing and 132 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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