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=0.929; PP4_Moderate: Detected in 1 PKU patient, primary BH4 deficiency excluded. Upgraded per ClinGen PAH EP. (PMID:23430918); PM3: Detected with c.1066-11G>A (P) (PMID:23430918). 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).
Met criteria codes
Detected in 1 PKU patient, primary BH4 deficiency excluded. Upgraded per ClinGen PAH EP.
Detected in 1 PKU patient: previously documented Phe level >360 umol/L and a Phe level >450 umol/L at the screening visit. Patients with a diagnosis of primary BH4 deficiency were excluded from the study.
Deleterious effect predicted in SIFT, Polyphen-2, MutationTaster. REVEL=0.929
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