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_001354304.2:c.277_280del

CA16020760

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 9f38374e-5cad-445a-a636-30c0aba9e978

HGVS expressions

NM_001354304.2:c.277_280del

NC_000012.12:g.102894810_102894813del

CM000674.2:g.102894810_102894813del

NC_000012.11:g.103288588_103288591del

CM000674.1:g.103288588_103288591del

NC_000012.10:g.101812718_101812721del

NG_008690.1:g.27793_27796del

NG_008690.2:g.68601_68604del

ENST00000553106.6:c.277_280del

ENST00000307000.7:c.262_265del

ENST00000546844.1:c.277_280del

ENST00000548677.2:n.364_367del

ENST00000548928.1:n.199_202del

ENST00000549111.5:n.373_376del

ENST00000550978.6:c.261_264del

ENST00000551337.5:c.277_280del

ENST00000551988.5:n.366_369del

ENST00000553106.5:c.277_280del

NM_000277.1:c.277_280del

NM_000277.2:c.277_280del

NM_001354304.1:c.277_280del

NM_000277.3:c.277_280del

Pathogenic

PVS1 PM3_Supporting PM2_Supporting PP4

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.277_280del (p.Asn93SerfsTer5) variant in PAH results in a frameshift in exon 3, with NMD predicted. It was reported in a Polish patient with classic PKU, with pathogenic variant p.R408W (PMID: 24350308). It is absent in gnomAD. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PP4, PM2_supporting, PM3_supporting.

PVS1

Frameshift variant in exon 3, NMD predicted

PM3_Supporting

detected with pathogenic variant p.R408W (c.1222C>T) parental testing not reported PMID: 24350308

PM2_Supporting

Absent from gnomAD

PP4

Detected in a Polish patient with classic PKU, BH4 deficiency not reportedly ruled out PMID: 24350308

Approved on: 2023-10-13

Published on: 2023-10-29

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