Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002233395 | SCV000832140 | uncertain significance | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2022-05-13 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 24 of the COL1A2 gene. It does not directly change the encoded amino acid sequence of the COL1A2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs369907691, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with COL1A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 579862). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Gene |
RCV001786412 | SCV002029050 | uncertain significance | not provided | 2021-05-25 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports a deleterious effect on splicing; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 579862; Landrum et al., 2016) |
Ambry Genetics | RCV002388324 | SCV002696787 | uncertain significance | Cardiovascular phenotype | 2021-06-25 | criteria provided, single submitter | clinical testing | The c.1404+4A>C intronic variant results from an A to C substitution 4 nucleotides after coding exon 24 in the COL1A2 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Baylor Genetics | RCV003333100 | SCV004041533 | uncertain significance | Osteogenesis imperfecta with normal sclerae, dominant form | 2023-05-11 | criteria provided, single submitter | clinical testing |