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]

Variant: NM_000277.3(PAH):c.617A>G (p.Tyr206Cys)

CA229660

102762 (ClinVar)

Gene: PAH (HGNC:5053)

Condition: phenylketonuria (MONDO:0009861)

Inheritance Mode: Autosomal recessive inheritance

UUID: 00b21724-fa72-4baa-ae3e-4292390ade23

Approved on: 2022-06-12

Published on: 2022-06-12

HGVS expressions

NM_000277.3(PAH):c.617A>G (p.Tyr206Cys)

NM_000277.3:c.617A>G

NC_000012.12:g.102855225T>C

CM000674.2:g.102855225T>C

NC_000012.11:g.103249003T>C

CM000674.1:g.103249003T>C

NC_000012.10:g.101773133T>C

NG_008690.1:g.67378A>G

NG_008690.2:g.108186A>G

ENST00000553106.6:c.617A>G

ENST00000307000.7:c.602A>G

ENST00000549111.5:n.713A>G

ENST00000553106.5:c.617A>G

NM_000277.1:c.617A>G

NM_000277.2:c.617A>G

NM_001354304.1:c.617A>G

NM_001354304.2:c.617A>G

Likely Pathogenic

PP4_Moderate PM3 PM2 PP3

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The NM_000277.3(PAH):c.617A>G (p.Tyr206Cys) missense variant has been reported in 1 patient with mild phenylketonuria (Phe = 914 umol/liter, BH4 deficiency excluded) (PP4_moderate; PMID: 29499199). This variant is absent from population databases (PM2), and is predicted deleterious by SIFT, Polyphen2, Mutation Taster. REVEL= 0.96 (PP3). This variant has been detected with pathogenic variants: p.Y204C (PMID: 16256386) and R241C (PMID: 26322415) (PM3). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4_moderate, PM2, PM3, PP3.

PP4_Moderate

PMID: 29499199 - Y206C detected in 1 patient with mild phenylketonuria (Phe = 914 umol/liter), BH4 deficiency excluded via urinary pterin analysis

PM3

PMID: 16256386 - Y206C detected with Y204C (reported as pathogenic in ClinVar; ClinVarID:590) in 1 Chinese patient with mild PKU; phase not confirmed, 0.5 points; PMID: 26322415 - Y206C detected with R241C in with Chinese patient (reported as pathogenic in ClinVar, VarID: 102803); parental DNA analyzed - Phase confirmed, 1.0 point

PM2

Variant absent from population databases.

PP3

Predicted deleterious in SIFT, Polyphen2, Mutation Taster. REVEL= 0.96.

Curation History

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.