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.842+3G>C

CA229814

102871 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: ad7649c8-a5c0-4598-8404-91fbd76346b9

HGVS expressions

NM_000277.2:c.842+3G>C

NM_000277.2(PAH):c.842+3G>C

NC_000012.12:g.102852812C>G

CM000674.2:g.102852812C>G

NC_000012.11:g.103246590C>G

CM000674.1:g.103246590C>G

NC_000012.10:g.101770720C>G

NG_008690.1:g.69791G>C

NG_008690.2:g.110599G>C

NM_000277.1:c.842+3G>C

NM_001354304.1:c.842+3G>C

NM_000277.3:c.842+3G>C

ENST00000307000.7:c.827+3G>C

ENST00000549247.6:n.601+3G>C

ENST00000553106.5:c.842+3G>C

ENST00000635477.1:n.3+3G>C

Likely Pathogenic

PM2 PP4_Moderate PM3_Strong

Evidence Links 4

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 in gnomAD+ExAC (MAF=0.00006). Absent from 1000G, ESP.; PP4_Moderate: Detected in Costa Rican and 1 Spanish PKU patients, exclusion of defects in tetrahydrobiopterine metabolism. (PMID:8860005; PMID:8981952); PM3_Strong: Detected in trans with I269L and R408W, known pathogenic variants. (PMID:9521426; PMID:23430918). 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: (PM2, PP4_Moderate, PM3_Strong).

PM2

Extremely low frequency in gnomAD+ExAC (MAF=0.00006). Absent from 1000G, ESP.

PP4_Moderate

Detected in Costa Rican and 1 Spanish PKU patients, exclusion of defects in tetrahydrobiopterine metabolism.

Detected on 4 Costa Rican classical PKU alleles. (IVS7nt3) PubMed:8860005

Detected in 1 Spanish PKU patient. Patients were considered as having PKU when the serum phenylalanine levels at diagnosis were >600 umol/liter and after exclusion of a defect in tetrahydrobiopterine metabolism. PubMed:8981952

PM3_Strong

Detected in trans with I269L and R408W, known pathogenic variants.

Patient F100: c.842+3g→c (IVS7nt3)/c.805A→C (I269L) (VarID 102842, Pathogenic). PubMed:9521426

Genotype: c.842+3G>C: p.R408W (VarID 577, Pathogenic) PubMed:23430918

Approved on: 2018-09-11

Published on: 2019-04-06

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.