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.785T>G (p.Val262Gly)

CA267671

120285 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 9357bfa1-6426-4f30-9c29-28a74e5240df

Approved on: 2018-12-10

Published on: 2019-04-05

HGVS expressions

NM_000277.2:c.785T>G

NM_000277.2(PAH):c.785T>G (p.Val262Gly)

NC_000012.12:g.102852872A>C

CM000674.2:g.102852872A>C

NC_000012.11:g.103246650A>C

CM000674.1:g.103246650A>C

NC_000012.10:g.101770780A>C

NG_008690.1:g.69731T>G

NG_008690.2:g.110539T>G

NM_000277.1:c.785T>G

NM_001354304.1:c.785T>G

NM_000277.3:c.785T>G

ENST00000307000.7:c.770T>G

ENST00000549247.6:n.544T>G

ENST00000553106.5:c.785T>G

Likely Pathogenic

PP3 PP4 PM3 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.785T>G (p.Val262Gly) variant in PAH is observed in 1 patient with classic PKU. BH4 deficiencies were not assessed. It was detected with a known pathogenic variant p.F39L. PMID: 26666653. This variant is absent from ExAC, gnomAD, 1000G, and ESP. It is predicted deleterious in SIFT, Polyphen-2, MutationTaster, and REVEL=0.954. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3, PP4, PP3.

PP3

Predicted deleterious in SIFT, Polyphen2, MutationTaster. REVEL=0.954

PP4

V262G observed in 1 patient with classic PKU. BH4 deficiencies not assessed. PMID: 26666653.

A total of 364 hyperphenylalaninemic patients, including 42 siblings, were investigated. According to their blood Phenylalanine concentration at time of diagnosis, these patients were assigned to one of the three phenotype categories. V262G was observed in 1 patient with classic PKU. PubMed:26666653

PM3

V262G detected with F39L, PMID: 26666653

c. [117C > G]; [785 T > G]/p. [Phe39Leu];[Val262Gly]. F39L, VarID 605, Pathogenic PubMed:26666653

PM2

Absent from ExAC, gnomAD, 1000G, ESP

PM5

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

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