Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
University of Washington Department of Laboratory Medicine, |
RCV005255887 | SCV005908177 | uncertain significance | Intellectual developmental disorder with gastrointestinal difficulties and high pain threshold | 2022-11-02 | criteria provided, single submitter | clinical testing | The p.Gly463fsArgfs*13 variant in the PPM1D gene has not been previously reported in association with disease. This variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). The p.Gly463fsArgfs*13 variant leads to a premature termination in the last exon of PPM1D. Premature termination at this location is not predicted to undergo nonsense-mediated decay, increasing the likelihood a truncated protein is made. These predictions have not been tested directly. Truncating variants in the last or penultimate exons of the PPM1D gene have been previously described in affected individuals. Using ACMG guidelines, this variant was classified as a variant of uncertain significance; however, there is suspicion that this variant could be associated with Jansen de Vries syndrome (ACMG evidence codes used: PVS1_strong, PM2_supporting). |