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.311C>A (p.Ala104Asp)

CA229515

102650 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 86ce59a8-cc5a-46f9-9b96-2254638db653

HGVS expressions

NM_000277.2:c.311C>A

NM_000277.2(PAH):c.311C>A (p.Ala104Asp)

NC_000012.12:g.102894776G>T

CM000674.2:g.102894776G>T

NC_000012.11:g.103288554G>T

CM000674.1:g.103288554G>T

NC_000012.10:g.101812684G>T

NG_008690.1:g.27827C>A

NG_008690.2:g.68635C>A

NM_000277.1:c.311C>A

NM_001354304.1:c.311C>A

NM_000277.3:c.311C>A

ENST00000307000.7:c.296C>A

ENST00000546844.1:c.311C>A

ENST00000548928.1:n.233C>A

ENST00000549111.5:n.407C>A

ENST00000550978.6:n.295C>A

ENST00000551337.5:c.311C>A

ENST00000551988.5:n.400C>A

ENST00000553106.5:c.311C>A

Pathogenic

PM3_Strong PS3 PM2

PP3

Evidence Links 2

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: PM2: Extremely low frequency: 0.00009 in gnomAD; PS3: 26% PAH enzyme activity; PM3_Strong: Detected with Y414C, pathogenic in ClinVar and V245L (P/LP) (PMID:9429153; PMID:24368688). In summary this variant meets criteria to be classified as pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PM2, PS3, PM3_Strong).

PM3_Strong

Detected with Y414C, pathogenic in ClinVar and V245L (P/LP)

Patient genotype: A104D/D222G (VarID 102775, clinical significance not provided). Patient genotype: Y414C (VarID 593, Pathogenic)/A104D. PubMed:9429153

ID #72: p.A104D/p.V245L (VarID 102810, Pathogenic/ likely pathogenic) PubMed:24368688

PS3

26% PAH enzyme activity

PM2

Extremely low frequency: 0.00009 in gnomAD

PP3

Conflicting predictions for pathogenicity: benign in Polyphen-2, disease causing in MutationTaster

Approved on: 2018-08-07

Published on: 2019-04-06

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