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.781C>G (p.Arg261Gly)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA269921

133314 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 4d9ea7aa-408e-4e3d-92b1-c2b52314fc06

Approved on: 2019-05-04

Published on: 2019-05-04

HGVS expressions

NM_000277.2:c.781C>G

NM_000277.2(PAH):c.781C>G (p.Arg261Gly)

NC_000012.12:g.102852876G>C

CM000674.2:g.102852876G>C

NC_000012.11:g.103246654G>C

CM000674.1:g.103246654G>C

NC_000012.10:g.101770784G>C

NG_008690.1:g.69727C>G

NG_008690.2:g.110535C>G

NM_000277.1:c.781C>G

NM_001354304.1:c.781C>G

NM_000277.3:c.781C>G

ENST00000307000.7:c.766C>G

ENST00000549247.6:n.540C>G

ENST00000553106.5:c.781C>G

Uncertain Significance

PM2 PP3

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.781C>G (p.Arg261Gly) variant in PAH has not been reported in the literature (to our knowledge). This variant is at extremely low frequency in gnomAD (MAF=0.00006, PM2). A deleterious effect is predicted in SIFT, Polyphen-2, MutationTaster, and REVEL=0.962. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP3.

PM2

extremely low frequency in gnomAD (MAF=0.00006)

PP3

Multiple lines of computational evidence support a deleterious effect (SIFT, PolyPhen2, MutationTaster, REVEL=0.962)

Curation History

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.