ClinVar Miner

Submissions for variant NM_000282.4(PCCA):c.415-2A>C (rs746286209)

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
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780576 SCV000917967 pathogenic Propionic acidemia 2021-02-16 criteria provided, single submitter clinical testing Variant summary: PCCA c.415-2A>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 3-prime acceptor site. Three predict the variant creates a new 3-prime acceptor site. The variant allele was found at a frequency of 8e-06 in 250414 control chromosomes (gnomAD). c.415-2A>C has been reported in the literature in compound heterozygosity with another pathogenic variant in at least one individual affected with Propionic Acidemia (e.g. Kraus_2012). This study also reported that the allele bearing c.415-2A>C is either not transcribed or the mRNA is degraded, and the authors measured approximately 2% of wild-type PCC activity in the patient's cells. No other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

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.