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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CA16020912

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: e16179cd-6cce-458b-b549-cf69c1d1bad0

HGVS expressions

NM_001354304.2:c.976del

NC_000012.12:g.102844425del

CM000674.2:g.102844425del

NC_000012.11:g.103238203del

CM000674.1:g.103238203del

NC_000012.10:g.101762333del

NG_008690.1:g.78178del

NG_008690.2:g.118986del

NM_000277.1:c.976del

NM_000277.2:c.976del

NM_001354304.1:c.976del

NM_000277.3:c.976del

ENST00000307000.7:c.961del

ENST00000549247.6:n.735del

ENST00000551114.2:n.638del

ENST00000553106.5:c.976del

ENST00000635477.1:n.80del

ENST00000635528.1:n.491del

Pathogenic

PP4 PM2 PVS1

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.976del (p.Trp326GlyfsTer15) variant in PAH is a null variant (frameshift variant) in a gene where LOF is a known mechanism of disease, leading to premature truncation and NMD (PVS1). It is absent from ethnically diverse control databases, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2). It has previously been reported in an Indian PKU case (blood Phe 439umol/L) (PMID: 24130151; PMID: 20188615) who was homozygous for the variant (PP4). Classification: Pathogenic Supporting criteria: PVS1, PM2; PP4

PP4

Single patient with Phe 439umol/L, homozygous c.976delT.

Single patient, homozygous for c.976delT with phe 439umol/L. PubMed:20188615

PM2

Not present in any population database.

PVS1

Single bp deletion results in a frameshift predicted to terminate the protein roughly 15aa from variant

Approved on: 2020-04-13

Published on: 2020-04-13

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