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.506G>A (p.Arg169His)

CA286505

102706 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 7b1098c0-cd76-4492-9b41-16cbd8f9ddc3

Approved on: 2018-08-10

Published on: 2019-04-06

HGVS expressions

NM_000277.2:c.506G>A

NM_000277.2(PAH):c.506G>A (p.Arg169His)

NC_000012.12:g.102866599C>T

CM000674.2:g.102866599C>T

NC_000012.11:g.103260377C>T

CM000674.1:g.103260377C>T

NC_000012.10:g.101784507C>T

NG_008690.1:g.56004G>A

NG_008690.2:g.96812G>A

NM_000277.1:c.506G>A

NM_001354304.1:c.506G>A

NM_000277.3:c.506G>A

ENST00000307000.7:c.491G>A

ENST00000549111.5:n.602G>A

ENST00000551988.5:n.530+10863G>A

ENST00000553106.5:c.506G>A

Likely Pathogenic

PM3_Strong PP4_Moderate

PP3 PM2

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

PAH-specific ACMG/AMP criteria applied: PP4_Moderate: This variant has been reported in multiple mild hyperphenylalaninaemia (MHP) patients, with BH4 defects excluded. Upgraded per ClinGen Metabolic workgroup. (PMID:10234516); PM3_Strong: Detected with P281L and A403V, both pathogenic variants (PMID:10234516). In summary this variant meets criteria to be classified as likely pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PP4_Moderate, PM3_Strong).

PM3_Strong

Detected with P281L and A403V, both pathogenic variants

Detected with p.P281L (Pathogenic in ClinVar). PubMed:10234516

PP4_Moderate

This variant has been reported in multiple mild hyperphenylalaninaemia (MHP) patients, with BH4 defects excluded. Upgraded per ClinGen Metabolic workgroup.

Found in patient with Mild Hyperphe., BH4 defect excluded. PubMed:10234516

PP3

Conflicting predictions of pathogenicity: Damaging in SIFT and MutationTaster, Benign in Polyphen2. REVEL=0.74

PM2

Absent from ESP and 1000G. AF ExAC (0.00026) and gnomAD (MAF= 0.00657, 1 homozygote).

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