Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • No ClinVar Id was directly found from the curated document

Variant: NM_000277.1:c.510-19_667del

CA16020833

Gene: PAH
Condition: phenylketonuria
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 7a382923-29c1-41c1-a7b6-c331affb9e93
Approved on: 2023-12-30
Published on: 2023-12-30

HGVS expressions

NM_000277.1:c.510-19_667del
NC_000012.12:g.102855177_102855353del
CM000674.2:g.102855177_102855353del
NC_000012.11:g.103248955_103249131del
CM000674.1:g.103248955_103249131del
NC_000012.10:g.101773085_101773261del
NG_008690.1:g.67252_67428del
NG_008690.2:g.108060_108236del
ENST00000553106.6:c.510-19_667del
ENST00000307000.7:c.495-19_652del
ENST00000549111.5:n.606-19_763del
ENST00000553106.5:c.510-19_667del
NM_000277.2:c.510-19_667del
NM_001354304.1:c.510-19_667del
NM_000277.3:c.510-19_667del
NM_001354304.2:c.510-19_667del
More

Pathogenic

Met criteria codes 4
PM3_Supporting PP4 PM2_Supporting PVS1

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen PAH Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Phenylketonuria VCEP
The c.510-19_667del variant in PAH involves part of exon 6, predicted to result in frameshift and NMD (PVS1). It has been reported in 1 individual with PKU. (PP4; PMID: 23842451). This variant is absent from gnomAD (PM2_supporting). This variant was detected with p.G272* (Pathogenic in ClinVar; PM3). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2_supporting, PM3_supporting, PP4.
Met criteria codes
PM3_Supporting
Detected with G272*, Pathogenic in ClinVar. Parental confirmation not reported.
Patient genotype: c.510-21_665del/G272* (VarID 596, Pathogenic) PubMed:23842451
PP4
c.510-21_665del was detected in one patient with Phe level 855. BH4 deficiency not reported/assessed. PMID: 23842451
Data were collected from 183 patients in six Dutch university medical centres. Blood Phe concentrations in dried blood spots were measured by the patients’ respective centre laboratory according to standard quantitative methods, with the same method per patient. c.510-21_665del was detected in one patient with Phe level 855 at baseline (T=0). PubMed:23842451
PM2_Supporting
Absent from ExAC, gnomAD, 1000G, ESP
PVS1
Partial exon deletion: His170, c.665 is codon 222 (Asp) HSF: Alteration of the WT acceptor site, most probably affecting splicing. MaxENT: 280-700% variation. Overlap with coding exons and predicted to undergo NMD: results in frameshift, percentage of exonic region overlapped: 11.63% (158/1359)
Curation History
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.
¤ Powered by BCM's Genboree.