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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CA16020838

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: fd94536c-59af-44ec-81e5-d4131b277ef8

HGVS expressions

NM_001354304.2:c.682G>T

NM_000277.1:c.682G>T

NM_000277.2:c.682G>T

NM_001354304.1:c.682G>T

NM_000277.3:c.682G>T

ENST00000307000.7:c.667G>T

ENST00000549111.5:n.778G>T

ENST00000553106.5:c.682G>T

NC_000012.12:g.102855160C>A

CM000674.2:g.102855160C>A

NC_000012.11:g.103248938C>A

CM000674.1:g.103248938C>A

NC_000012.10:g.101773068C>A

NG_008690.1:g.67443G>T

NG_008690.2:g.108251G>T

Pathogenic

PM2 PVS1 PP4

PM3

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The nonsense variant c.682G>T (p.Glu228Ter) 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 reported in at least one compound heterozygous patient with classical PKU (PMID: 24401910), in trans with VUS variant Val190Gly. In summary, this variant meets criteria to be classified as Pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4.

PM2

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

PVS1

The Glu228Ter nonsense variant creates a stop codon in exon 6 of 13 which is predicted to cause NMD.

PP4

A taiwanese patient with classical PKU (Phe>1200 μmol /l) was described in PMID: 24401910. BH4 deficiency was reportedly ruled out but the methods were not described.

PM3

The patient from PMID: 24401910 is compound heterozygous for this nonsense variant, Glu228Ter, and the missense variant Val190Gly (no classification available at this time), unknown if trans phase was confirmed.

Approved on: 2020-10-30

Published on: 2020-10-30

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