Submissions for variant NM_005027.4(PIK3R2):c.160G>A (p.Val54Met)

gnomAD frequency: 0.00242  dbSNP: rs201370957

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Brain Malformations Variant Curation Expert Panel	RCV001725188	SCV001960885	benign	Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes	2022-02-11	reviewed by expert panel	curation	The c.160G>A (NM_005027.4) variant in PIK3R2 is a missense variant predicted to cause substitution of (p.Val54Met). The highest population minor allele frequency in gnomAD v2.1.1 is 0.004092 in the European (non Finnish) population, which is higher than the ClinGen BMEP threshold ([>=0.00185]) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as Benign for mosaic autosomal dominant overgrowth with or without cerebral malformations due to abnormalities in MTOR-pathway genes based on the ACMG/AMP criteria applied, as specified by the ClinGen Brain Malformations Expert Panel: BA1; -8 points (VCEP specifications version 1; Approved: 1/31/2021)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000551536	SCV000644904	benign	Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1	2024-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001573664	SCV001906910	benign	not provided	2018-10-30	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001573664	SCV002009741	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001573664	SCV004145223	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	PIK3R2: BS2
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573664	SCV001799879	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001700409	SCV001923314	benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003935468	SCV004753441	benign	PIK3R2-related disorder	2021-06-28	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).