ClinGen Dosage Sensitivity Curation Page
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COL1A2
- Curation Status: Complete
- id: ISCA-22424
- Date last evaluated: 2012-10-12
- Issue Type: ClinGen Gene Curation
- Gene type: protein-coding
- ClinGen: Search for information about COL1A2 at clinicalgenome.org
- Entrez Gene: https://www.ncbi.nlm.nih.gov/gene/1278
- OMIM: https://omim.org/entry/120160
- Gene Reviews: https://www.ncbi.nlm.nih.gov/books/NBK1295/?term=COL1A2
- ClinGen Haploinsufficiency Score: 0
- ClinGen Triplosensitivity Score: 0
- ExAC pLI score: 1.0
- Haploinsufficiency score: 0
- Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
Haploinsufficiency phenotype comments:
Heterozygous COL1A2 mutations are associated with osteogenesis imperfecta types II-IV (MIM# 166210, 259420, 166220) and Ehlers-Danlos syndrome, type VIIB (MIM #130060). The vast majority of reported COL1A2 mutations, including intragenic copy number changes, result in a structurally abnormal protein product and pathogenesis by a dominant-negative, rather than a dosage sensitivity-type, mechanism (see PMID 17078022 and OMIM for reviews). Any identified copy number changes within this gene will need specific scrutiny to determine potential pathogenesis. Homozygous and compound heterozygous null COL1A2 mutations are associated with the autosomal recessive condition, Ehlers-Danlos syndrome, cardiac valvular form (MIM #225320). When reported, carrier parents had no evidence of valvular heart disease.
- Triplosensitivity score: 0
- Strength of Evidence (disclaimer): No evidence for dosage pathogenicity