Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000727324 | SCV000574424 | uncertain significance | not provided | 2017-04-01 | criteria provided, single submitter | clinical testing | The c.2171G>A variant in the NPHP3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.2171G>A 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.2171G>A may decrease the natural splice donor site in exon 15. However, in the absence of RNA/functional studies, the actual effect of the c.2171G>A change in this individual is unknown. If c.2171G>A does not alter splicing, it will result in the R724N missense change. The R724N 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 not conserved. 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.2171G>A as a variant of uncertain significance. |
| EGL Genetic Diagnostics, |
RCV000727324 | SCV000707559 | uncertain significance | not provided | 2017-04-07 | criteria provided, single submitter | clinical testing |