• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
COL2A1 (HGNC:2200) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
collagen type II alpha 1 chain
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
SEDC, AOM
Alias symbols
STL1
%HI
2.04(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.13(Read more about gnomAD LOEUF score)
Cytoband
12q13.11
Genomic Coordinates
GRCh37/hg19: chr12:48366750-48398259 NCBI Ensembl UCSC
GRCh38/hg38: chr12:47972967-48006212 NCBI Ensembl UCSC
MANE Select Transcript
NM_001844.5 ENST00000380518.8 (Read more about MANE Select)
Function
Type II collagen is specific for cartilaginous tissues. It is essential for the normal embryonic development of the skeleton, for linear growth and for the ability of cartilage to resist compressive forces. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-27355
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
07/29/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 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.
  • PUBMED: 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.
  • PUBMED: 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.
HI Evidence Comments:
Variants in COL2A1 have been associated with a number of autosomal dominant disorders (see OMIM IDs above and GeneReviews https://www.ncbi.nlm.nih.gov/books/NBK540447/). For this review we have focused on evidence pertaining to Stickler Syndrome, Type 1 (OMIM ID: 108300).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000012.11) (NC_000012.12)