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

Variant: NM_000277.1:c.197_204del

CA16021007

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: af0e89ef-9142-4204-831b-dc5c37c6c154

HGVS expressions

NM_000277.1:c.197_204del

NC_000012.12:g.102894883_102894890del

CM000674.2:g.102894883_102894890del

NC_000012.11:g.103288661_103288668del

CM000674.1:g.103288661_103288668del

NC_000012.10:g.101812791_101812798del

NG_008690.1:g.27713_27720del

NG_008690.2:g.68521_68528del

ENST00000553106.6:c.197_204del

ENST00000307000.7:c.182_189del

ENST00000546844.1:c.197_204del

ENST00000548677.2:n.284_291del

ENST00000548928.1:n.119_126del

ENST00000549111.5:n.293_300del

ENST00000550978.6:n.181_188del

ENST00000551337.5:c.197_204del

ENST00000551988.5:n.286_293del

ENST00000553106.5:c.197_204del

ENST00000635500.1:n.165_172del

NM_000277.2:c.197_204del

NM_001354304.1:c.197_204del

NM_000277.3:c.197_204del

NM_001354304.2:c.197_204del

Pathogenic

PVS1 PM3_Supporting PM2 PP4_Moderate

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.197_204del8 (p.Glu66Alafs*8) variant in PAH has been reported in 1 individual with PAH deficiency (BH4 deficiency excluded, PP4_Moderate; PMID: 21147011). This variant was detected with p.A300S (Pathogenic in ClinVar) (PM3_supporting; PMID: 21147011). It is a frameshift variant predicted to lead to NMD (PVS1). It is absent from gnomAD (PM2). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PP4_Moderate, PM3, PM2.

PVS1

Frameshift

PM3_Supporting

Detected with A300S (pathogenic in ClinVar) PMID: 21147011 parental analysis not confirmed

Allele 1:p.D75X, Allele 2: p.A300S (VarID92751, Pathogenic) PubMed:21147011

PM2

absent from gnomAD v2.1.1

PP4_Moderate

c.197-204del8 was detected on 1 patient (called D75X). BH4 defects assessed. PMID: 21147011

588 hyperphenylalaninemic patients were investigated. Assessment included PAH gene and genes of the BH4 synthesis/recycling pathways (PTS and QDPR). c.197-204del8 was detected on 1 patient (called D75X). PubMed:21147011

Approved on: 2022-06-28

Published on: 2022-06-28

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