ClinVar Miner

Submissions for variant NM_005027.4(PIK3R2):c.1126A>G (p.Lys376Glu)

dbSNP: rs886041591
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000394419 SCV000330281 pathogenic not provided 2023-07-31 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26860062, 26520804)
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV003236667 SCV003935184 pathogenic Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 2023-06-26 criteria provided, single submitter clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV005250045 SCV005900708 pathogenic PIK3R2-related disorder 2023-12-26 criteria provided, single submitter clinical testing The c.1126A>G (p.Lys376Glu) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. This variant has been previously reported as a heterozygous change in patients with polymicrogyria (PMID: 26520804, 33057194, 37486637). The c.1126A>G (p.Lys376Glu) variant is located in the SH2 domain, which is a known hotspot domain for pathogenic variations associated with polymicrogyria (PMID: 26520804). The c.1126A>G (p.Lys376Glu) variant is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, c.1126A>G (p.Lys376Glu) is classified as Pathogenic.
Yale Center for Mendelian Genomics, Yale University RCV001849360 SCV002106993 pathogenic Seizure 2021-04-05 no assertion criteria provided literature only

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