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: PVS1: Nonsense variant; PM2: Extremely low frequency in gnomAD. MAF=0.00002.; PP4_Moderate: Detected in 3 chromosomes of patients with PAH deficiency. BH4 deficiency ruled out. (PMID:8268925). In summary this variant meets criteria to be classified as pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PVS1, PM2, PP4_Moderate).
Met criteria codes
Detected in 3 chromosomes of patients with PAH deficiency. BH4 deficiency ruled out.
W187X detected in 3 chromosomes. All patients were presenting with blood phenylalanine levels persistently above 150 umol/l, and diagnosis of PAH deficiency was made when other potential causes of hyperphenylalaninemia had been ruled out. The criteria for inclusion were: normal serum tyrosine, normal urinary excresion of biopterin and neopterin, and no indication of acquired hyperphenylalaninemia.
Extremely low frequency in gnomAD. MAF=0.00002.
Approved on: 2018-08-10
Published on: 2019-04-06
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