Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001372239 | SCV001568853 | uncertain significance | Glycogen storage disease IXa1 | 2020-05-26 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Gly300 amino acid residue in PHKA2. Other variant(s) that disrupt this residue have been observed in individuals with PHKA2-related conditions (PMID: 28627441, 21646031), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PHKA2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with serine at codon 300 of the PHKA2 protein (p.Gly300Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. |
| Ce |
RCV003458034 | SCV004184876 | likely pathogenic | not provided | 2023-11-01 | criteria provided, single submitter | clinical testing | PHKA2: PM2, PM5, PP3, PP4 |