COL2A1 |
- 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
- 0.18(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
ClinGen Curation ID:
CCID:006905
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:
- Stickler syndrome type 1 Monarch
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)