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.843-2A>T

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA229816

102873 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 0f80f747-69bd-4d63-9cca-27ccf00298b5

Approved on: 2019-04-09

Published on: 2019-04-09

HGVS expressions

NM_000277.2:c.843-2A>T

NM_000277.2(PAH):c.843-2A>T

NC_000012.12:g.102851758T>A

CM000674.2:g.102851758T>A

NC_000012.11:g.103245536T>A

CM000674.1:g.103245536T>A

NC_000012.10:g.101769666T>A

NG_008690.1:g.70845A>T

NG_008690.2:g.111653A>T

NM_000277.1:c.843-2A>T

NM_001354304.1:c.843-2A>T

NM_000277.3:c.843-2A>T

ENST00000307000.7:c.828-2A>T

ENST00000549247.6:n.602-2A>T

ENST00000551114.2:n.503A>T

ENST00000553106.5:c.843-2A>T

ENST00000635477.1:n.4-2A>T

Pathogenic

PM2 PVS1 PP4

PM3

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.843-2A>T variant in PAH has been reported in 1 homozygote individual with classic PKU (PMID: 9452062). This variant disrupts the canonical splice acceptor site of intron 8 where LOF is a known mechanism of disease, exon skipping disrupts reading frame, and is predicted to undergo NMD. Coding exon 8 is present in biologically-relevant transcript. This variant is absent from population databases, including: 1000 Genomes, ESP, and gnomAD. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4.

PM2

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

PVS1

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

PP4

reported in a patient with classic PKU, BH4 deficiency not reported/assessed. PMID: 9452062

PM3

detected in the homozygous state

Curation History

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