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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CA16020988

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 79c72b03-7607-46a8-a596-c2c597940a6b

HGVS expressions

NM_001354304.2:c.1271T>A

NM_000277.1:c.1271T>A

NM_000277.2:c.1271T>A

NM_001354304.1:c.1271T>A

NM_000277.3:c.1271T>A

ENST00000307000.7:c.1256T>A

ENST00000551114.2:n.933T>A

ENST00000553106.5:c.1271T>A

ENST00000635477.1:n.375T>A

ENST00000635528.1:n.786T>A

NC_000012.12:g.102840444A>T

CM000674.2:g.102840444A>T

NC_000012.11:g.103234222A>T

CM000674.1:g.103234222A>T

NC_000012.10:g.101758352A>T

NG_008690.1:g.82159T>A

NG_008690.2:g.122967T>A

Pathogenic

PVS1 PP4 PM2

PM3

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1271T>A (p.Leu424*) variant in PAH meets criteria to be classified as pathogenic. PAH-specific ACMG/AMP criteria applied: PM2: Absent from population databases (1000 Genomes, ExAC). PVS1: Nonsense mutation, causing early termination of exon 12. NMD is predicted to occur. PP4: Patient has classic PKU (PMID:24350308).PM3_Supporting: Found to co-occur with PAH EX5del4232ins268 in one patient with classic PKU, but no additional studies to demonstrate phase of variants. No other PAH variants identified in patient (PMID:24350308). Not predicted to be responsive to BH4 (PMID:24350308)

PVS1

Nonsense mutation, variant is predicted to undergo NMD

PP4

Patient has classic PKU

PubMed:24350308

PM2

Absent from population databases.

PM3

Co-occured with PAH EX5del4232ins268 (aka g.47563_51794del4232g.56161_56430ins268) in patient with classic PKU. This variant is currently unclassified. No additional testing to prove phase.

Approved on: 2020-08-07

Published on: 2020-08-07

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