ClinVar Miner

Submissions for variant NM_001844.5(COL2A1):c.258C>A (p.Cys86Ter) (rs794727261)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000255165 SCV000227235 pathogenic not provided 2017-11-13 criteria provided, single submitter clinical testing
GeneDx RCV000255165 SCV000322315 pathogenic not provided 2018-04-20 criteria provided, single submitter clinical testing The C86X pathogenic variant in the COL2A1 gene has previously been reported in association with Stickler syndrome and segregation with disease has been observed in multiple affected relatives from unrelated families (Donoso et al., 2002; Parma et al., 2002; Tran-Viet et al., 2013). This variant is described as being associated with a high incidence of ocular involvement and a lower incidence of the systemic features associated with Stickler syndrome (Donoso et al., 2002; Parma et al., 2002). In addition, C86X has been identified in two unrelated probands at GeneDx with features associated with Stickler syndrome, and it segregated with retinal disease in one individual's parent. Furthermore, C86X has been classified in ClinVar as a pathogenic variant by another clinical laboratory (ClinVar SCV000227235.3; Landrum et al., 2016), and it is not observed in large population cohorts (Lek et al., 2016).The C86X variant is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Many other nonsense variants in the COL2A1 gene have been reported in Human Gene Mutation Database in association with Stickler syndrome (Stenson et al., 2014). Of note, this variant is located in exon 2, which is an alternatively spliced exon. A genotype-phenotype correlation of variants in exon 2 with a predominantly ocular phenotype has been proposed due to differential tissue expression of alternative isoforms (Donoso et al., 2003; Robin et al., 2017).In summary, C86X in the COL2A1 gene is interpreted as a pathogenic variant.
Fulgent Genetics,Fulgent Genetics RCV000762897 SCV000893297 pathogenic Achondrogenesis type II; Avascular necrosis of the head of femur; Epiphyseal dysplasia, multiple, with myopia and conductive deafness; Coxa plana; Kniest dysplasia; Osteoarthritis with mild chondrodysplasia; Spondyloperipheral dysplasia-short ulna syndrome; Stickler syndrome type 1; Platyspondylic dysplasia, Torrance type; Spondylometaphyseal dysplasia; Spondyloepiphyseal dysplasia congenita; Czech dysplasia, metatarsal type; Stickler syndrome, type I, nonsyndromic ocular; Spondyloepiphyseal dysplasia, stanescu type 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000255165 SCV001202292 pathogenic not provided 2020-01-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys86*) in the COL2A1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals and families affected with Stickler syndrome (PMID: 12429249, 23592912, 28559085). ClinVar contains an entry for this variant (Variation ID: 195148). Loss-of-function variants in COL2A1 are known to be pathogenic (PMID: 20179744). For these reasons, this variant has been classified as Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.