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]

Variant: NM_000277.2(PAH):c.155delT (p.Leu52Cysfs)

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA267691

120310 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: b11f0c2c-5a8b-487b-9d9a-3d3012444a43

Approved on: 2019-04-03

Published on: 2019-08-16

HGVS expressions

NM_000277.2(PAH):c.155delT (p.Leu52Cysfs)

NC_000012.12:g.102912805del

CM000674.2:g.102912805del

NC_000012.11:g.103306583del

CM000674.1:g.103306583del

NC_000012.10:g.101830713del

NG_008690.1:g.9799del

NG_008690.2:g.50607del

ENST00000553106.6:c.155del

ENST00000307000.7:c.140del

ENST00000546844.1:c.155del

ENST00000548677.2:n.242del

ENST00000548928.1:n.77del

ENST00000549111.5:n.251del

ENST00000550978.6:c.139del

ENST00000551337.5:c.155del

ENST00000551988.5:n.244del

ENST00000553106.5:c.155del

ENST00000635500.1:n.123del

NM_000277.1:c.155del

NM_000277.2:c.155del

NM_001354304.1:c.155del

NM_000277.3:c.155del

NM_001354304.2:c.155del

Pathogenic

PVS1 PP4 PM2

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.155delT (p.Leu52Cysfs) is a frameshift variant in exon 2 of 13 in PAH, predicted to undergo nonsense mediated decay with the truncated region critical to protein function. It has been reported in 1 individual with PKU (BH4 deficiency not excluded), who carried a second nonsense variant in PAH (PP4; PMID: 26666653 ). This variant is absent from population databases (PM2). In summary, this variant meets our criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4.

PVS1

Frameshift variant in exon 2 of 13 in PAH, predicted to undergo nonsense mediated decay with the truncated region critical to protein function

PP4

This variant was reported in a patient with PKU who carried a second nonsense mutation in PAH (Arg261*), however BH4 deficiency was not ruled out. PubMed:26666653

PM2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

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