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]

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Variant: NM_000277.2(PAH):c.802T>C (p.Tyr268His)

CA229773

102841 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: f094cb35-0851-4c83-aa5c-5feea8816db1

HGVS expressions

NM_000277.2:c.802T>C

NM_000277.2(PAH):c.802T>C (p.Tyr268His)

NC_000012.12:g.102852855A>G

CM000674.2:g.102852855A>G

NC_000012.11:g.103246633A>G

CM000674.1:g.103246633A>G

NC_000012.10:g.101770763A>G

NG_008690.1:g.69748T>C

NG_008690.2:g.110556T>C

NM_000277.1:c.802T>C

NM_001354304.1:c.802T>C

NM_000277.3:c.802T>C

ENST00000307000.7:c.787T>C

ENST00000549247.6:n.561T>C

ENST00000553106.5:c.802T>C

Uncertain Significance

PP3 PM2

PM5

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.802T>C (p.Tyr268His) variant in PAH has not been reported in the literature to our knowledge. The reference in BioPKU/PAHdb (Eisensmith, 1996) does not include this variant. It is absent from ExAC, 1000G, and ESP, with Extremely low frequency in gnomAD (0.000004063). A deleterious effect is predicted in SIFT, Polyphen2, MutationTaster, and REVEL=0.977. . In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP3.

PP3

Deleterious effect predicted in SIFT, Polyphen2, MutationTaster. REVEL=0.977.

PM2

Absent from ExAC, 1000G, ESP. Extremely low frequency in gnomAD ( 0.000004063)

PM5

This is the only variant found in this codon in ClinVar.

Approved on: 2018-12-10

Published on: 2019-04-05

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