The PIK3CA c.3203dup (p.Asn1068LysfsTer5; p.N1068Kfs*5) variant has been observed in somatic cancers in COSMIC (COSV55878665, 29 occurrences) and has also been reported in ClinVar as Likely pathogenic with criteria provided by a single submitter.
The variant was absent from both gnomAD v2.1 and gnomAD v4.1, supporting PM2 at the Brain Malformations VCEP supporting level and arguing against BA1, BS1, and BS2 population-based benign evidence.
The affected residue lies at Asn1068, and the Brain Malformations specification Table 4 lists a PIK3CA critical domain spanning amino acids 797-1068, supporting PM1_Supporting; however, although OncoKB and the literature triage point to likely gain-of-function biology, the workspace does not provide variant-specific validated assay details sufficient to adjudicate PS3.
SpliceAI predicts no significant splice impact for this variant (max delta score 0.03), but PP3 is not applicable in this gain-of-function VCEP and BP4/BP7 are restricted to synonymous, intronic, or UTR contexts rather than coding frameshift variants.
