Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000494217 | SCV000582224 | uncertain significance | not provided | 2017-05-08 | criteria provided, single submitter | clinical testing | The c.1064 C>A variant in the SDCCAG8 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.1064 C>A variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). One in-silico splice prediction model predicts that c.1064 C>A destroys the splice donor site for exon 9, which is expected to cause abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of the c.1064 C>A change in this individual is unknown. If c.1064 C>A does not alter splicing, it will result in the T355N missense change. The T355N variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret c.1064 C>A as a variant of uncertain significance. |
| Invitae | RCV002524031 | SCV003026160 | uncertain significance | Senior-Loken syndrome 7; Bardet-Biedl syndrome 16 | 2022-01-01 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 429612). This variant has not been reported in the literature in individuals affected with SDCCAG8-related conditions. This variant is present in population databases (rs199524638, gnomAD 0.009%). This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 355 of the SDCCAG8 protein (p.Thr355Asn). |