Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001449428 | SCV001652544 | likely benign | PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome | 2019-10-01 | criteria provided, single submitter | clinical testing | |
| Genetic Services Laboratory, |
RCV001820140 | SCV002071139 | likely benign | not specified | 2020-03-02 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the PURA gene demonstrated a sequence change, c.306C>T, in exon 1 which does not result in an amino acid change. This sequence change does not appear to have been previously described in patients with PURA-related intellectually disability. This particular sequence change has been described in the gnomAD database in one individual which corresponds to a population frequency of 0.00041% (rs762714935). This sequence change is not clearly predicted to have a deleterious effect on splicing based on in silico splice prediction programs. As the c.306C>T sequence change does not result in a change in the PURA amino acid sequence, it is possible that this change is non-pathogenic and represents a benign sequence variant of the PURA gene, however functional studies have not been performed to prove this conclusively. De novo heterozygous pathogenic variants in the PURA gene have been described in individuals with a neurodevelopmental phenotype characterized by hypotonia, global developmental delay including language impairment, feeding difficulties, intellectual disability, and frequent apnea and epilepsy (OMIM# 616158 and PMID: 29150892). Subsequent targeted analysis of the ANKRD11 gene demonstrates the presence of the above sequence change in the individual’s unaffected mother. The presence of the above sequence change in a phenotypically normal individual is indicative of this sequence change being a likely benign sequence change. |