ClinVar Miner

Submissions for variant NM_000292.3(PHKA2):c.869G>A (p.Arg290His)

gnomAD frequency: 0.00002  dbSNP: rs186632999
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001249715 SCV001423740 uncertain significance Glycogen storage disease IXa1 2019-11-26 criteria provided, single submitter clinical testing The PHKA2 c.869G>A (p.Arg290His) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search in relation to phosphorylase kinase deficiency. The p.Arg290His variant is reported at a frequency of 0.000076 in the African population of the Genome Aggregation Database (gnomAD), but this is based on one allele in a region of good sequence coverage, so the variant is presumed to be rare. In addition, this variant has been observed in a hemizygote state in one individual in gnomAD, but adults with the associated phosphorylase kinase deficiency may be asymptomatic (Kishani et al. 2019). Based on the limited evidence, the p.Arg290His variant is classified as a variant of unknown significance for PHKA2-related phosphorylase kinase deficiency.
Labcorp Genetics (formerly Invitae), Labcorp RCV001249715 SCV003034139 uncertain significance Glycogen storage disease IXa1 2022-07-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 290 of the PHKA2 protein (p.Arg290His). This variant is present in population databases (rs186632999, gnomAD 0.008%). 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: 973283). 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: "Benign"; Align-GVGD: "Class C0"). 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV005232220 SCV005875626 uncertain significance not provided 2024-06-11 criteria provided, single submitter clinical testing The PHKA2 c.869G>A; p.Arg290His variant (rs186632999), to our knowledge, is not reported in the medical literature in a PHKA2 related disorder but is reported in ClinVar (Variation ID: 973283). This variant is found in the general population with an overall allele frequency of 0.001% (2/183,366 alleles, including 1 hemizygote) in the Genome Aggregation Database (v2.1.1). Computational analyses predict that this variant is deleterious (REVEL: 0.829). Due to limited information, the clinical significance of this variant is uncertain at this time.

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