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]

Link to SEPIO compliant JSON-LD document

CA16020720

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 1eae3b8a-7f13-4ed6-a03c-e9edf537ff1d

HGVS expressions

NM_000277.1:c.48dup

NC_000012.12:g.102917083dup

CM000674.2:g.102917083dup

NC_000012.11:g.103310861dup

CM000674.1:g.103310861dup

NC_000012.10:g.101834991dup

NG_008690.1:g.5520dup

NG_008690.2:g.46328dup

NM_000277.2:c.48dup

NM_001354304.1:c.48dup

NM_000277.3:c.48dup

ENST00000307000.7:c.-100dup

ENST00000546844.1:c.48dup

ENST00000547319.1:n.359dup

ENST00000549111.5:n.144dup

ENST00000550978.6:n.32dup

ENST00000551337.5:c.48dup

ENST00000551988.5:n.137dup

ENST00000553106.5:c.48dup

ENST00000635500.1:n.29-4185dup

Pathogenic

PM3_Supporting PP4 PM2 PVS1

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

Pathogenic: The c.48dup (p.D17*) variant has been reported in one individual with classic PKU, who carried a second pathogenic variant in PAH (p.L48S) (PM3, PP4; PMID: 18299955). This variant is absent from gnomAD, 1000 Genomes, and ESP databases (PM2). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM3-supporting, PM2, PP4.

PM3_Supporting

This variant was detected in a patient with classic PKU phenotype, who carried a second PAH variant (p.L48S). PMID: 18299955. Parental analysis not reported.

This variant was detected in a patient with classic PKU phenotype, who carried a second PAH variant (p.L48S). PubMed:18299955

PP4

This variant was detected in a patient with classic PKU phenotype. The patients were tested for the exclusion of lacking the cofactor BH4 for the differential characterization of the cause for the absent of PAH. PMID: 18299955

PM2

absent from gnomAD

PVS1

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

Approved on: 2019-08-11

Published on: 2019-08-11

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.