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_000277.3(PAH):c.745del (p.Leu249fs)

CA16020850

370982 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 1c9d8c70-9dfc-4355-8ef0-9cc1b939866f

HGVS expressions

NM_000277.3:c.745del

NM_000277.3(PAH):c.745del (p.Leu249fs)

NC_000012.12:g.102852912del

CM000674.2:g.102852912del

NC_000012.11:g.103246690del

CM000674.1:g.103246690del

NC_000012.10:g.101770820del

NG_008690.1:g.69691del

NG_008690.2:g.110499del

ENST00000553106.6:c.745del

ENST00000307000.7:c.730del

ENST00000549247.6:n.504del

ENST00000553106.5:c.745del

NM_000277.1:c.745del

NM_000277.2:c.745del

NM_001354304.1:c.745del

NM_001354304.2:c.745del

Pathogenic

PP4 PM2 PM3_Supporting PVS1

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.745del (p.Leu249fs) variant in PAH has been reported in 1 Chilean patient with mild PKU; Phe = 600-900umol/L (PMID: 29288420; PP4). This variant was detected with V388M - reported at Pathogenic in ClinVar (VarID:610, 7 submitters); phase not confirmed - 0.5 points (PMID: 29288420; PM3_supporting). This frameshift variant is predicted to undergo NMD, not located in last exon or last 50bp of preliminary exon (Coding exon number 7 out of 13 coding exons; 7 out of total exons) (PVS1). This variant is absent from population databases (PM2). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4, PM3_supporting.

PP4

PMID: 29288420 - L249fs detected in 1 Chilean patient with mild PKU; Phe = 600-900umol/L

PM2

Variant absent from population databases.

PM3_Supporting

PMID: 29288420 - L249fs detected with V388M - reported at Pathogenic in ClinVar (VarID:610, 7 submitters); phase not confirmed - 0.5 points

PVS1

Frameshift variant, predicted to undergo NMD, not located in last exon or last 50bp of preliminary exon. Coding exon number 7 out of 13 coding exons (7 out of total exons).

Approved on: 2021-05-15

Published on: 2021-12-12

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.