The c.1173A>G (NM_006218.4) variant in PIK3CA is a missense variant predicted to cause substitution of (p.Ile391Met). This variant resides within the kinase domain of PIK3CA that is defined as a critical functional domain by the ClinGen BMEP (PMIDs: 26637981, 24459181, 27631024) (PM1_Supporting). The highest population minor allele frequency in gnomAD v2.1.1 is 0.2113 in African/African American population, which is higher than the ClinGen BMEP threshold ([>=0.00185]) for BA1, and therefore meets this criterion (BA1). This variant was identified the homozygous state in >3 individuals within control databases (BS2). PIK3CA, in which the variant was identified, is defined by the ClinGen Brain Malformations Expert Panel as a gene that has a low rate of benign missense variation and where pathogenic missense variants are a common mechanism of disease (PP2). 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: PM1_P, BA1, BS2, PP2; -10 points (VCEP specifications version 1; Approved: 1/31/2021)