NM_006218.4:c.412G>T (p.Asp138Tyr; p.D138Y) is absent from gnomAD v2.1 and gnomAD v4.1, which supports PM2 at supporting strength under the Brain Malformations specification.
gnomad_v4 ↗PIK3CA is missense constrained, and the gnomAD missense z-score is 8.75, which is greater than the PP2 threshold of 3.09 defined in the specification.
Asp138 is outside the PIK3CA adaptor-binding domain (amino acids 31-108), Ras-binding domain (173-292), and kinase domains (322-483 and 797-1068) listed in Table 4, so PM1 is not supported.
ClinVar does not contain this variant, and no case-level, segregation, or functional evidence sufficient for PS1, PS2, PS3, PS4, PM5, BS3, PP1, BP2, or BP5 was available.
clinvar ↗With PM2_supporting and PP2_supporting alone, the variant is classified as a variant of uncertain significance.
