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.842+1G>T

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA229812

102869 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 61b0c352-14e1-4d67-8509-3390ab16ec24

Approved on: 2019-04-09

Published on: 2019-04-09

HGVS expressions

NM_000277.2:c.842+1G>T

NM_000277.2(PAH):c.842+1G>T

NC_000012.12:g.102852814C>A

CM000674.2:g.102852814C>A

NC_000012.11:g.103246592C>A

CM000674.1:g.103246592C>A

NC_000012.10:g.101770722C>A

NG_008690.1:g.69789G>T

NG_008690.2:g.110597G>T

NM_000277.1:c.842+1G>T

NM_001354304.1:c.842+1G>T

NM_000277.3:c.842+1G>T

ENST00000307000.7:c.827+1G>T

ENST00000549247.6:n.601+1G>T

ENST00000553106.5:c.842+1G>T

ENST00000635477.1:n.3+1G>T

Pathogenic

PM2 PVS1 PP4

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The PAH c.842+1G>T variant has been reported at least once in the literature in a 15 month old patient with moderate PKU in the homozygote state (PP4, PMID: 23220018). This variant is absent from 1000G, ESP, and gnomAD databases. This variant disrupts the canonical splice donor site of intron 7 where LOF is a known mechanism of disease, exon skipping disrupts reading frame, and is predicted to undergo NMD. Coding exon 7 is present in biologically-relevant transcript. In summary, this variant meets criteria to be pathogenic. PAH-specific ACMG/AMP criteria applied: PM2, PP4, PVS1.

PM2

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

PVS1

Canonical splicing site variant. Donor site of intron 7.

PP4

Reported as IVS7+1G>T in a patient with mild PKU.

Patient 14 (Table 2) in the homozygote state with mild PKU. PubMed:23220018

Curation History

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