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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CA1139532590

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: bbdff8c0-4e9b-4d1f-aa34-07027c9399eb

Approved on: 2020-10-16

Published on: 2020-10-16

HGVS expressions

NM_001354304.2:c.543_545del

NM_000277.1:c.543_545del

NM_000277.2:c.543_545del

NM_001354304.1:c.543_545del

NM_000277.3:c.543_545del

ENST00000307000.7:c.528_530del

ENST00000549111.5:n.639_641del

ENST00000551988.5:n.564_566del

ENST00000553106.5:c.543_545del

NC_000012.12:g.102855300_102855302del

CM000674.2:g.102855300_102855302del

NC_000012.11:g.103249078_103249080del

CM000674.1:g.103249078_103249080del

NC_000012.10:g.101773208_101773210del

NG_008690.1:g.67304_67306del

NG_008690.2:g.108112_108114del

Likely Pathogenic

PM4 PM2 PP4_Moderate PM3_Supporting

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

This c.543_545del (p.Glu182del) variant in PAH was reported in a patient with moderate PKU. BH4 enzyme deficiency was ruled out by analysis of urinary pterins and DHPR activity. This variant is observed with pathogenic variant c.611A>G, phase is unknown (PMID: 28754886). The variant is absent from controls in population databases. This in-frame deletion changes the protein length in a non-repeat region. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM4, PP4_moderate, and PM3_supporting.

PM4

This in-frame deletion changes the protein length in a non-repeat region.

PM2

This variant is absent from controls in ExAC, 1000 Genomes, and gnomAD population databases.

PP4_Moderate

This variant was observed in one patient with moderate PKU (Phe=900 µmol/L). Patients with defect in the synthesis and recycling of BH4 were excluded by analysis of urinary pterins and dihydropteridine reductase activity in erythrocytes. PMID: 28754886

PubMed:28754886

PM3_Supporting

c.[611A>G];[541-543delGAG]. Phase is unknown. PMID:28754886

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