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]

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CA16020970

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 66e02e7e-b8c3-4033-828b-04cc081ba5c4

HGVS expressions

NM_001354304.2:c.1205T>G

NM_000277.1:c.1205T>G

NM_000277.2:c.1205T>G

NM_001354304.1:c.1205T>G

NM_000277.3:c.1205T>G

ENST00000307000.7:c.1190T>G

ENST00000551114.2:n.867T>G

ENST00000553106.5:c.1205T>G

ENST00000635477.1:n.309T>G

ENST00000635528.1:n.720T>G

NC_000012.12:g.102840510A>C

CM000674.2:g.102840510A>C

NC_000012.11:g.103234288A>C

CM000674.1:g.103234288A>C

NC_000012.10:g.101758418A>C

NG_008690.1:g.82093T>G

NG_008690.2:g.122901T>G

Uncertain Significance

PM2 PP3 PP4_Moderate

PM5

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1205 (p.Phe402Cys) variant in PAH has been detected in 1 Japanese patient with mild HPA and BH4 deficiency excluded (PMID: 21307867; PP4_Moderate). This variant is absent from population databases (PM2), and is predicted deleterious by SIFT, PolyPhen2, MutationTaster, and REVEL = 0.94 (PP3). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP3, PP4_Moderate.

PM2

Variant absent from population databases.

PP3

Predicted deleterious by SIFT, PolyPhen2, MutationTaster, and REVEL = 0.94.

PP4_Moderate

PMID: 21307867 - F402C detected in 1 Japanese patient with mild HPA, serum Phe = 180-600umol/l. BH4 deficiency was excluded by analysis of dihydropteridine reductase activity in red blood cells, biopterin loading test and/or pteridine analysis in urine.

PubMed:21307867

PM5

At same codon as c.1204T>A (p.F402I), c.1204T>C (p.F402L), and c.1204T>G (p.F402V) - all curated as VUS by ClinGen PAH VCEP.

Approved on: 2020-08-27

Published on: 2020-08-27

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