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

CA16020815

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 81580d4c-89e3-47cf-85d8-7a582d06d614

HGVS expressions

NM_001354304.2:c.551del

NC_000012.12:g.102855294del

CM000674.2:g.102855294del

NC_000012.11:g.103249072del

CM000674.1:g.103249072del

NC_000012.10:g.101773202del

NG_008690.1:g.67312del

NG_008690.2:g.108120del

NM_000277.1:c.551del

NM_000277.2:c.551del

NM_001354304.1:c.551del

NM_000277.3:c.551del

ENST00000307000.7:c.536del

ENST00000549111.5:n.647del

ENST00000551988.5:n.572del

ENST00000553106.5:c.551del

Pathogenic

PVS1 PP4_Moderate PM2

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The frameshift variant c.551del generates a stop codon in exon 6 of 13 and is predicted to undergo NMD. The variant is absent from population databases, including gnomAD. It has been in at least one HPA patient (PMID: 21307867). In summary, this variant meets criteria to be classified as Pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4_moderate.

PVS1

The frameshift variant c.551del occurs in exon 6 where it generates a premature stop codon and is thus predicted to cause NMD.

PP4_Moderate

At least one patient from PMID: 21307867 meets criteria for PP4_moderate with PHE levels of >0.18 mM and exclusion of BH4 deficiency.

PubMed:21307867

PM2

The variant is absent from population databases, including gnomAD, ExAC, 1000 Genomes, and ESP.

Approved on: 2020-10-30

Published on: 2020-10-30

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