ClinVar Miner

Submissions for variant NM_005027.4(PIK3R2):c.1217G>A (p.Arg406His)

gnomAD frequency: 0.00008  dbSNP: rs201531496
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003238383 SCV002009742 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001768436 SCV003249027 uncertain significance Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 2023-12-15 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 406 of the PIK3R2 protein (p.Arg406His). This variant is present in population databases (rs201531496, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with PIK3R2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1319057). 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 not expected to disrupt PIK3R2 protein function with a negative predictive value of 80%. 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.

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