Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001234308 | SCV001406946 | pathogenic | Achondrogenesis, type IB; Atelosteogenesis type II; Multiple epiphyseal dysplasia type 4; Diastrophic dysplasia | 2023-10-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu474Cysfs*12) in the SLC26A2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 266 amino acid(s) of the SLC26A2 protein. This variant is present in population databases (rs780990131, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with diastrophic dysplasia (PMID: 11241838). ClinVar contains an entry for this variant (Variation ID: 960730). This variant disrupts a region of the SLC26A2 protein in which other variant(s) (p.Lys575Serfs*10) have been determined to be pathogenic (PMID: 7923357, 8528239, 8571951). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003473804 | SCV004201744 | likely pathogenic | Achondrogenesis, type IB | 2023-09-07 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003987803 | SCV004803313 | pathogenic | Osteochondrodysplasia | 2024-01-13 | criteria provided, single submitter | clinical testing | Variant summary: SLC26A2 c.1421delT (p.Leu474CysfsX12) results in a premature termination codon, predicted to cause a truncation of the protein. Variants downstream of this position have been classified as pathogenic by our laboratory (example, c.1724delA p.Lys575SerfsX10). The variant allele was found at a frequency of 8e-06 in 251270 control chromosomes. c.1421delT has been reported in the literature in individual(s) affected with Diastrophic Dysplasia, however, no sufficient information was provided for further analysis (example, Rossi_2001). These report(s) do not provide unequivocal conclusions about association of the variant with Sulfate Transporter-Related Osteochondrodysplasia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 11241838). ClinVar contains an entry for this variant (Variation ID: 960730). Based on the evidence outlined above, the variant was classified as Pathogenic. |