Please note this is a beta version of the ClinGen Evidence Repository. This resource is intended to provide access to variant level evidence used and applied by ClinGen Variant Curation Expert Panels in the classification of variants. In this beta version, the evidence is limited to curation notes and referenced literature (PMIDs).
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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 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).
Detected with c.611A>G (P/LP) and R408W (P). Upgraded per ClinGen SVI workgroup.
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