ClinVar Miner

Submissions for variant NM_000532.5(PCCB):c.1498+2T>C (rs879253816)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Medical Genetics and Genomics,Sir Ganga Ram Hospital RCV000237038 SCV000256891 pathogenic Propionic acidemia criteria provided, single submitter research
Fulgent Genetics,Fulgent Genetics RCV000237038 SCV000893636 pathogenic Propionic acidemia 2018-10-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000237038 SCV001360759 pathogenic Propionic acidemia 2019-02-28 criteria provided, single submitter clinical testing Variant summary: The variant, PCCB c.1498+2T>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 5' splicing donor site. The variant was absent in 246010 control chromosomes (gnomAD) but has been reported in the literature in multiple homozygous individuals affected with severe Propionic Acidemia (Desviat 2006, Gupta 2016). These data indicate that the variant is very likely to be associated with disease. One of these studies also reported, based on cDNA sequence analysis from patients' fibroblasts, that the variant causes skipping of exon 14, resulting in a frameshift; qPCR quantification demonstrated less than 0.1% of the normal PCCB transcripts in these patients (Desviat 2006). No 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.