ClinVar Miner

Submissions for variant NM_000292.3(PHKA2):c.884G>A (p.Arg295His)

dbSNP: rs797044877
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000190690 SCV000244131 pathogenic Inborn genetic diseases 2014-10-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000694745 SCV000823203 pathogenic Glycogen storage disease IXa1 2023-03-01 criteria provided, single submitter clinical testing This variant disrupts the p.Arg295 amino acid residue in PHKA2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12862311, 23578772, 31508908; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PHKA2 protein function. ClinVar contains an entry for this variant (Variation ID: 208676). This missense change has been observed in individuals with glycogen storage disease type IX (PMID: 10330341, 27103379, 28627441). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 295 of the PHKA2 protein (p.Arg295His).
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000694745 SCV003806433 likely pathogenic Glycogen storage disease IXa1 2023-01-31 criteria provided, single submitter clinical testing A hemizygous missense variation in exon 9 of the PHKA2 gene that results in the amino acid substitution of Histidine for Arginine at codon 295 (p.Arg295His) was detected. The p.Arg295His variant has not been reported in the 1000 genomes and gnomAD databases. The in silico predictions of the variant are probably damaging by PolyPhen-2 (HumDiv) and damaging by SIFT, LRT and MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as likely pathogenic.
GeneReviews RCV003328098 SCV004035035 not provided Glycogen storage disease IXd no assertion provided literature only

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