ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000012.11) (NC_000012.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
27390512 In 2016, Wang et al. used Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) on 16 individuals with Stickler syndrome to identify potential variants in COL2A1 and COL11A1. Analysis identified 5 variants in COL2A1 in 6 of these individuals. These variants included 1 nonsense variant and 2 small deletions. 1 proband with a small deletion also had 2 affected family members with the same variant. Another proband with a small deletion had 1 other affected family member with the variant. Additionally, the proband with the nonsense variant was a confirmed de novo case.
27408751 In 2016, Kondo et al. used PCR and sequencing on 40 patients from 23 families with Stickler syndrome to identify potential variants in COL2A1. Analysis identified 17 variants in COL2A1 in 21 of the families. Of these variants, there were 5 nonsense variants, 3 splice site variants (a 4th splice site variant was identified, but the significance was unclear), and 8 intragenic deletion variants. Per the authors, "All of the mutations were predicted to lead to a premature termination of the gene, resulting in haploinsufficiency of type II collagen." 7 of the variants were sporadic, with 2 being confirmed de novo.
17721977 In 2008, McAlinden et al. used PCR on 2 unrelated individuals with ocular Stickler syndrome. The authors identified 1 nonsense variant in both individuals (p.Cys64Stop) and believe that this variant causes either nonsense-mediated decay or nonsense-mediated altered splicing.

Haploinsufficiency phenotype comments:

Variants in COL2A1 have been associated with a number of autosomal dominant disorders (see OMIM IDs above and GeneReviews For this review we have focused on evidence pertaining to Stickler Syndrome, Type 1 (OMIM ID: 108300).

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity