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.740G>A (p.Gly247Asp)

CA229734

102817 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 0a85343d-4608-4067-8252-1f3bf74f3cf0

HGVS expressions

NM_000277.2:c.740G>A

NM_000277.2(PAH):c.740G>A (p.Gly247Asp)

NC_000012.12:g.102852917C>T

CM000674.2:g.102852917C>T

NC_000012.11:g.103246695C>T

CM000674.1:g.103246695C>T

NC_000012.10:g.101770825C>T

NG_008690.1:g.69686G>A

NG_008690.2:g.110494G>A

NM_000277.1:c.740G>A

NM_001354304.1:c.740G>A

NM_000277.3:c.740G>A

ENST00000307000.7:c.725G>A

ENST00000549247.6:n.499G>A

ENST00000553106.5:c.740G>A

Uncertain Significance

PP3 PP4 PM2

PM5

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.740G>A (p.Gly247Asp) variant in PAH was reported in 2 patients with classic PKU. PMID: 20920871. This varant is predicted deleterious in SIFT, Polyphen2, MutationTaster, and REVEL=0.975. It has an extremely low frequency in ExAC/gnomAD (MAF 0.00003). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP4, PP3.

PP3

Predicted deleterious in SIFT, Polyphen2, MutationTaster. REVEL=0.975

PP4

Seen in 2 patients with classic PKU. PMID: 20920871

124 unrelated families with classic PKU, corresponding to 248 independent alleles, from different regions of Iran were enrolled. DNA from the subjects and their families. In families with more than one person with PKU, only one of them was included. G247D was detected in 2 unrelated patients in the homozygous state. PubMed:20920871

PM2

Extremley low frequency in ExAC/gnomAD (MAF 0.00003)

PM5

G247V Likely Pathogenic

Approved on: 2018-12-10

Published on: 2019-04-06

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