ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.169-1G>A

dbSNP: rs1877439517
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV001269074 SCV001448298 pathogenic Phenylketonuria 2020-10-15 reviewed by expert panel curation This c.169-1G>A (aka IVS2-1G>A) variant in PAH has been observed in at least two patients with PAH deficiency (PMID: 18294361 and 30159852) in trans with pathogenic variant c.168+5G>C. One patient was homozygous for this variant (PMID: 30159852). This variant is absent in controls from population databases. This variant in the -1 splice acceptor site of intron 2 results in exon skipping or use of a cryptic splice site. The variant disrupts the reading frame and is predicted to undergo nonsense mediated decay. This variant breaks the splice site in intron 2 according to computational models. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PM3, and PP4.

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. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.