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_000277.2(PAH):c.176A>G (p.Asp59Gly)

CA229468

102616 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 67b0c9a7-1a39-4ab6-a4c6-f15a393519b4

HGVS expressions

NM_000277.2:c.176A>G

NM_000277.2(PAH):c.176A>G (p.Asp59Gly)

NC_000012.12:g.102894911T>C

CM000674.2:g.102894911T>C

NC_000012.11:g.103288689T>C

CM000674.1:g.103288689T>C

NC_000012.10:g.101812819T>C

NG_008690.1:g.27692A>G

NG_008690.2:g.68500A>G

NM_000277.1:c.176A>G

NM_001354304.1:c.176A>G

NM_000277.3:c.176A>G

ENST00000307000.7:c.161A>G

ENST00000546844.1:c.176A>G

ENST00000548677.2:n.263A>G

ENST00000548928.1:n.98A>G

ENST00000549111.5:n.272A>G

ENST00000550978.6:n.160A>G

ENST00000551337.5:c.176A>G

ENST00000551988.5:n.265A>G

ENST00000553106.5:c.176A>G

ENST00000635500.1:n.144A>G

Uncertain Significance

PM2

PP3 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.176A>G (p.Asp59Gly) variant in PAH has not been reported in the literature to our knowledge. A reference from BioPKU/PAHdb is not located (Carducci C, 1999). It is absent from ExAC, gnomAD, 1000G, and ESP. There are conflicting predictions of pathogenicity: SIFT/Polyphen2: benign; MutationTaster: Damaging; REVEL=0.565. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2.

PM2

Absent from ExAC, gnomAD, 1000G, ESP

PP3

Conflicting predictions of pathogenicity: SIFT/Polyphen2:benign, MutationTaster: Damaging. REVEL=0.565

PM5

D59Y, no interpretation in ClinVar

Approved on: 2018-12-10

Published on: 2019-04-06

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