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PAH-specific ACMG/AMP criteria applied: PM2: Absent from ExAC, gnomAD, 1000G, ESP; PP3: Deleterious effect predicted in SIFT, Polyphen-2, MutationTaster. REVEL=0.966; PP4_Moderate: Detected in PKU patients. BH4 deficiency assessed. Upgraded per ClinGen PAH EP. (PMID:26600521; PMID:23430918); PM3_Strong: Detected with c.611A>G (P/LP) and R408W (P). Upgraded per ClinGen SVI workgroup. (PMID:23430918; PMID:26600521). In summary this variant meets criteria to be classified as likely pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PM2, PP3, PP4_Moderate, PM3_Strong).
Met criteria codes
Deleterious effect predicted in SIFT, Polyphen-2, MutationTaster. REVEL=0.966
Absent from ExAC, gnomAD, 1000G, ESP
Detected with c.611A>G (P/LP) and R408W (P). Upgraded per ClinGen SVI workgroup.
Detected in PKU patients. BH4 deficiency assessed. Upgraded per ClinGen PAH EP.
Phe>120 uM, no BH4 defect, in trans with EX6-96G>A
Detected in 1 PKU patient: PKU (>450 umol/L).
Approved on: 2018-08-10
Published on: 2019-05-04
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