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.913-8A>G

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Curation History
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CA267687

120295 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: e60e7a9c-b110-4bf6-9220-7244d3e1a56b

Approved on: 2019-11-08

Published on: 2019-11-08

HGVS expressions

NM_000277.2:c.913-8A>G

NM_000277.2(PAH):c.913-8A>G

NC_000012.12:g.102846959T>C

CM000674.2:g.102846959T>C

NC_000012.11:g.103240737T>C

CM000674.1:g.103240737T>C

NC_000012.10:g.101764867T>C

NG_008690.1:g.75644A>G

NG_008690.2:g.116452A>G

NM_000277.1:c.913-8A>G

NM_001354304.1:c.913-8A>G

NM_000277.3:c.913-8A>G

ENST00000307000.7:c.898-8A>G

ENST00000549247.6:n.672-8A>G

ENST00000551114.2:n.575-8A>G

ENST00000553106.5:c.913-8A>G

ENST00000635477.1:n.74-2528A>G

ENST00000635528.1:n.420A>G

Uncertain Significance

PP4 PM3 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.913-8A>G PAH variant has been identified in at least one patient with classic PKU (PMID: 26666653). It was detected in trans with the pathogenic variant c.1315+1G>A (ClinVar 576). This variant is absent from 1000G, ESP, and gnomAD databases. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PM3.

PP4

A compound heterozygous proband with the c.913-8A>G variant was described with the classic PKU phenotype and PHE >1200umol/L. Defects in BH4 cofactor metabolism were not excluded.

A compound heterozygous proband with the c.913-8A>G variant was described with the classic PKU phenotype and PHE >1200umol/L. Defects in BH4 cofactor metabolism were not excluded. PubMed:26666653

PM3

The c.913-8A>G intronic variant has been observed in trans with the previously assessed pathogenic variant c.1315+1G>A (ClinVar 576, Pathogenic).

The c.913-8A>G intronic variant has been observed in trans with the previously assessed pathogenic variant c.1315+1G>A (ClinVar 576, Pathogenic). PubMed:26666653

PM2

The variant is absent from ExAC, gnomAD, 1000G, and ESP.

Curation History

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