Submissions for variant NM_005027.4(PIK3R2):c.1955G>A (p.Arg652Gln)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV003408794	SCV004115666	uncertain significance	PIK3R2-related disorder	2023-01-31	criteria provided, single submitter	clinical testing	The PIK3R2 c.1955G>A variant is predicted to result in the amino acid substitution p.Arg652Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-18279682-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003649455	SCV004550747	uncertain significance	Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1	2023-04-06	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. 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. This variant has not been reported in the literature in individuals affected with PIK3R2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 652 of the PIK3R2 protein (p.Arg652Gln).