Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001209837 | SCV001381289 | pathogenic | Glycogen storage disease IXa1 | 2023-07-14 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu1142Valfs*61) in the PHKA2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 94 amino acid(s) of the PHKA2 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PHKA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 940284). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts a region of the PHKA2 protein in which other variant(s) (p.Pro1205Leu) have been determined to be pathogenic (PMID: 7847371, 9870210, 21646031, 21911307, 24055370, 25266922, 28468868). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |