ClinVar Miner

Submissions for variant NM_005027.4(PIK3R2):c.1243G>A (p.Ala415Thr)

gnomAD frequency: 0.00025  dbSNP: rs200178501
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001724574 SCV001949721 benign not provided 2018-10-15 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001821965 SCV002065906 benign not specified 2021-11-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002543872 SCV002993242 uncertain significance Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 2022-10-07 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. ClinVar contains an entry for this variant (Variation ID: 1296705). This variant has not been reported in the literature in individuals affected with PIK3R2-related conditions. This variant is present in population databases (rs200178501, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 415 of the PIK3R2 protein (p.Ala415Thr).
Ambry Genetics RCV002543871 SCV003732081 likely benign Inborn genetic diseases 2021-12-03 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.
PreventionGenetics, part of Exact Sciences RCV003948693 SCV004765006 likely benign PIK3R2-related disorder 2020-10-21 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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