ClinVar

Description

Variant summary: SLC26A2 c.1535C>A (p.Thr512Lys) results in a non-conservative amino acid change located in the SLC26A/SulP transporter domain (IPR011547) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.8e-05 in 251120 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in SLC26A2 causing Sulfate Transporter-Related Osteochondrodysplasia (4.8e-05 vs 0.003), allowing no conclusion about variant significance. c.1535C>A has been reported in the literature in multiple individuals affected with diastrophic dysplasia (DTD) (example: Bonafe_2008). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect resulted in sulfate transporter activity similar to non-transfected cells or transfected with the vector alone (example: Bonafe_2008). The following publication has been ascertained in the context of this evaluation (PMID: 18708426). ClinVar contains an entry for this variant (Variation ID: 4099). Based on the evidence outlined above, the variant was classified as pathogenic.