Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

CA16020832

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: dd2f6143-fa77-4772-babc-2d24929caa57

HGVS expressions

NM_000277.3:c.659A>C

NM_000277.1:c.659A>C

NM_000277.2:c.659A>C

NM_001354304.1:c.659A>C

NM_001354304.2:c.659A>C

ENST00000307000.7:c.644A>C

ENST00000549111.5:n.755A>C

ENST00000553106.5:c.659A>C

NC_000012.12:g.102855183T>G

CM000674.2:g.102855183T>G

NC_000012.11:g.103248961T>G

CM000674.1:g.103248961T>G

NC_000012.10:g.101773091T>G

NG_008690.1:g.67420A>C

NG_008690.2:g.108228A>C

Likely Pathogenic

PM2 PP4_Moderate PM3_Strong

PP3

Evidence Links 2

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.659A>C (p.His220Pro) variant in PAH has been reported in 3 individuals with MHP or classic PKU (BH4 deficiency excluded, PMID 26322415 ) detected in trans with pathogenic variant p.R241C in 2 patients (PMID: 30050108). This variant is absent in population databases. Computational evidence is conflicting. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PM3_strong.

PM2

Absent from controls in ExAC, gnomAD, 1000 Genomes, or ESP

PP4_Moderate

PMID 26322415: listed p.[A156P];[H220P] in one patient with classic PKU (Phe levels >20mg/dl). All patients fulfilled the diagnostic criteria of PKU, with a blood phenylalanine concentration >2mg/dl. BH4 deficiency was excluded byanalysis of urinary pterins and dihydropteridine reductase activity in erythrocytes.

PM3_Strong

PMID 26322415: detected with p.[A156P] no interpretation in ClinVar and p.R241C (P 8 submitters, 2 patients) PMID: 30050108. All mutations identified in patients were confirmed by analyzing parental DNA. When mutation loci were detected in patients, the same locus of the parental sample was amplified by PCR and analyzed by Sanger automated sequencing.

PubMed:30050108

PP3

Conflicting predictions

Approved on: 2020-03-08

Published on: 2020-03-08

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.