COL2A1 has been described in association with autosomal dominant Achondrogenesis type II, a severe disorder affecting cartilage and bone development. Comstock et al. described Achondrogenesis type II in 2010 as being "characterized by severe micromelic dwarfism with small chest and prominent abdomen, incomplete ossification of the vertebral bodies, and disorganization of the costochondral junction". At least 15 unique variants have been identified in patients (PMIDs: 17994563, 7741714, 7829510, 7757081, 10797431, 31392067, 25823796, 31299979). Evidence supporting this gene-disease relationship includes case-level and experimental data. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. In summary, COL2A1 is definitively associated with autosomal dominant Achondrogenesis type II. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the Skeletal Disorders Gene Curation Expert Panel on 10/5/2020. Gene Clinical Validity Standard Operating Procedures (SOP) - Version 7.
COL2A1 has been described in association with autosomal dominant Achondrogenesis type II, a severe disorder affecting cartilage and bone development. Comstock et al. described Achondrogenesis type II in 2010 as being "characterized by severe micromelic dwarfism with small chest and prominent abdomen, incomplete ossification of the vertebral bodies, and disorganization of the costochondral junction". Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found differences in molecular mechanisms and phenotypic variability. Therefore, the following disease entities have been split into multiple disease entities, COL2A1-related spondyloepiphyseal dysplasia (OMIM:609162, OMIM:183900, OMIM:184254, OMIM:184250), dysplasia of the proximal femoral epiphyses (OMIM:608805, OMIM:150600), spondyloperipheral dysplasia (OMIM:271700), Stickler syndrome type 1 (OMIM:108300), Kniest dysplasia (OMIM:156550), Achondrogenesis type II (OMIM:200610), and platyspondylic skeletal dysplasia, Torrance type (OMIM:151210). The split curations have been curated separately. At least 15 unique variants have been identified in patients (PMIDs: 17994563, 7741714, 7829510, 7757081, 10797431, 31392067, 25823796, 31299979). Evidence supporting this gene-disease relationship includes case-level and experimental data. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. In summary, COL2A1 is definitively associated with autosomal dominant Achondrogenesis type II. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the Skeletal Disorders Gene Curation Expert Panel on 10/5/2020. Gene Clinical Validity Standard Operating Procedures (SOP) - Version 7.
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