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

Variant: NM_001354304.2:c.75del

CA16020726

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 64839d6f-7c44-4068-93c5-e2c060c6e72b

HGVS expressions

NM_001354304.2:c.75del

NC_000012.12:g.102912885del

CM000674.2:g.102912885del

NC_000012.11:g.103306663del

CM000674.1:g.103306663del

NC_000012.10:g.101830793del

NG_008690.1:g.9719del

NG_008690.2:g.50527del

ENST00000553106.6:c.75del

ENST00000307000.7:c.60del

ENST00000546844.1:c.75del

ENST00000548677.2:n.162del

ENST00000549111.5:n.171del

ENST00000550978.6:c.59del

ENST00000551337.5:c.75del

ENST00000551988.5:n.164del

ENST00000553106.5:c.75del

ENST00000635500.1:n.43del

NM_000277.1:c.75del

NM_000277.2:c.75del

NM_001354304.1:c.75del

NM_000277.3:c.75del

Pathogenic

PVS1 PM3_Supporting PM2_Supporting PP4

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.75del (p.Ile25MetfsTer13) variant in PAH results in a frameshift in exon 2, with NMD predicted. It was reported in a Chinese patient with hyperphenylalaninemia, with pathogenic variant p.Gln419Arg (PMID: 25456745). It is absent in gnomAD. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PP4, PM2_supporting, PM3_supporting.

PVS1

Frameshift variant in exon 2, NMD predicted

PM3_Supporting

detected with Gln419Arg (P/LP in ClinVar, P by PAH VCEP), parental analysis not reported

PM2_Supporting

absent from gnomAD

PP4

Reported in a Chinese patient with HPA (blood Phe > 120 umol/L) PMID: 25456745

Approved on: 2023-10-13

Published on: 2023-10-13

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