Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000489111 | SCV000576686 | uncertain significance | not provided | 2017-04-21 | criteria provided, single submitter | clinical testing | The c.1586A>G variant in the GPHN gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.1586A>G variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In-silico splice prediction models predict that c.1586A>G may create a cryptic splice donor site in exon 16 that could supplant the natural splice donor site. However, in the absence of RNA/functional studies, the actual effect of the c.1586A>G change in this individual is unknown. If c.1586A>G does not alter splicing, it will result in the N529S missense change. The N529S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret c.1586A>G as a variant of uncertain significance. |