Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588352 | SCV000695415 | likely pathogenic | Sulfate transporter-related osteochondrodysplasia | 2022-07-14 | criteria provided, single submitter | clinical testing | Variant summary: SLC26A2 c.1707C>G (p.Tyr569X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251228 control chromosomes. To our knowledge, no occurrence of c.1707C>G in individuals affected with Sulfate Transporter-Related Osteochondrodysplasia and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Another laboratory classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV000809074 | SCV000949213 | pathogenic | Achondrogenesis, type IB; Atelosteogenesis type II; Multiple epiphyseal dysplasia type 4; Diastrophic dysplasia | 2018-11-15 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the SLC26A2 protein. Other variant(s) that disrupt this region (p.Lys575Serfs*10) have been determined to be pathogenic (PMID: 8571951, 8528239). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with SLC26A2-related disease. ClinVar contains an entry for this variant (Variation ID: 495551). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the SLC26A2 gene (p.Tyr569*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 171 amino acids of the SLC26A2 protein. |
| Baylor Genetics | RCV003471936 | SCV004201792 | likely pathogenic | Achondrogenesis, type IB | 2022-12-12 | criteria provided, single submitter | clinical testing |