Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002024171 | SCV002308588 | likely pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 264 of the COL1A2 protein (p.Lys264Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant osteogenesis imperfecta (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 1518853). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the c.792G nucleotide in the COL1A2 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 31737030). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |