ClinVar

Description

The SLC26A2 c.1987G>A (p.Gly663Arg) missense variant was reported in one fetus in a compound heterozygous state with a second missense variant. The patient was diagnosed with an intermediate phenotype between diastrophic dysplasia and atelosteogenesis, type II. The unaffected mother of the patient was a carrier of the p.Gly663Arg variant, which was absent in 48 healthy controls (Maeda et al. 2006). No patients were reported with achondrogenesis, multiple epiphyseal dysplasia or sulfate transporter-related osteochondrodysplasia. The p.Gly663Arg variant is not found in the 1000 Genomes Project, the Exome Sequencing Project, Exome Aggregation Consortium, or the Genome Aggregation Database, in a region with good sequence coverage and hence is presumed to be rare. Functionally, Maeda et al. (2006) showed that in HEK293 cells, the p.Gly663Arg variant protein was located within the cytoplasm as compared to wild type protein which was present along the plasma membrane of the cell, with no cytoplasmic or nuclear staining. Based on the evidence, the p.Gly663Arg variant is classified as a variant of unknown significance but suspicious for pathogenicity for SLC26A2-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.