ClinVar Miner

Submissions for variant NM_000292.3(PHKA2):c.1576G>A (p.Asp526Asn)

gnomAD frequency: 0.00003  dbSNP: rs778051353
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000686726 SCV000814255 uncertain significance Glycogen storage disease IXa1 2023-08-07 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 526 of the PHKA2 protein (p.Asp526Asn). This variant is present in population databases (rs778051353, gnomAD 0.009%). This missense change has been observed in individual(s) with clinical features of glycogen storage disease type IXa and/or ketotic hypoglycemia symptoms (PMID: 34117828; Invitae). ClinVar contains an entry for this variant (Variation ID: 566810). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PHKA2 protein function. 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.
Fulgent Genetics, Fulgent Genetics RCV000686726 SCV002814384 uncertain significance Glycogen storage disease IXa1 2021-08-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV002547105 SCV003742896 likely benign Inborn genetic diseases 2021-09-01 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Clinical Genetics Laboratory, University Hospital Schleswig-Holstein RCV000686726 SCV002011749 uncertain significance Glycogen storage disease IXa1 2021-06-18 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004754530 SCV005360117 uncertain significance PHKA2-related disorder 2024-06-04 no assertion criteria provided clinical testing The PHKA2 c.1576G>A variant is predicted to result in the amino acid substitution p.Asp526Asn. This variant has been reported in an individual with ketotic hypoglycemia; however, a similarly affected family member did not carry the variant (Benner et al 2021. PubMed ID: 34117828). This variant is reported in 0.0087% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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