Spondyloepiphyseal dysplasia congenita: genes and variants

Genes linked to Spondyloepiphyseal dysplasia congenita

• 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.

  38 disease-causing and 11 uncertain variants in COL2A1 are linked to Spondyloepiphyseal dysplasia congenita.

Known disease-causing variants in Spondyloepiphyseal dysplasia congenita

Which prediction tools work for Spondyloepiphyseal dysplasia congenita

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

• AlphaMissense: 100 out of 100
• EVE: 100 out of 100
• MutPred2: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 94 out of 100
• PolyPhen-2: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Achondrogenesis type II is also caused by COL2A1 variants; they fall mostly in different places as the Spondyloepiphyseal dysplasia congenita variants (34 disease-causing).
• Stickler syndrome is also caused by COL2A1 variants; they fall mostly in different places as the Spondyloepiphyseal dysplasia congenita variants (26 disease-causing).
• Spondyloepimetaphyseal dysplasia, Strudwick type is also caused by COL2A1 variants; they fall mostly in different places as the Spondyloepiphyseal dysplasia congenita variants (18 disease-causing).
• Connective tissue disorder is also caused by COL2A1 variants; they fall mostly in different places as the Spondyloepiphyseal dysplasia congenita variants (15 disease-causing).
• Type 2 collagenopathy is also caused by COL2A1 variants; they fall mostly in different places as the Spondyloepiphyseal dysplasia congenita variants (14 disease-causing).

Diseases related to Spondyloepiphyseal dysplasia congenita

• 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
• Type 2 collagenopathy, 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 Spondyloepiphyseal dysplasia congenita?

In CATVariant, Spondyloepiphyseal dysplasia congenita is linked to 1 analyzed protein: COL2A1 (Collagen alpha-1(II) chain).

How many genetic variants are linked to Spondyloepiphyseal dysplasia congenita?

59 variants: 38 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 11 are of uncertain significance or have conflicting reports.

Which uncertain variants in Spondyloepiphyseal dysplasia congenita 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 Spondyloepiphyseal dysplasia congenita?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 1.00, based on 28 disease-causing and 9 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.

Download every variant as CSV · Browse all diseases · Methods · About the Center