Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002586580 | SCV002935631 | uncertain significance | Senior-Loken syndrome 7; Bardet-Biedl syndrome 16 | 2023-05-22 | criteria provided, single submitter | clinical testing | This sequence change affects codon 140 of the SDCCAG8 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SDCCAG8 protein. This variant also falls at the last nucleotide of exon 4, which is part of the consensus splice site for this exon. This variant is present in population databases (rs763284045, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with SDCCAG8-related conditions. 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1903732). |
Prevention |
RCV004529153 | SCV004111241 | uncertain significance | SDCCAG8-related disorder | 2023-11-20 | criteria provided, single submitter | clinical testing | The SDCCAG8 c.420G>T variant is predicted to result in the amino acid substitution p.Lys140Asn. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.075% of alleles in individuals of East Asian descent in gnomAD, which is more common than expected for an undocumented disease-causing variant. Although we suspect this variant may be benign, at this time, the clinical significance is uncertain due to the absence of conclusive functional and genetic evidence. |