Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Integrated Genetics/Laboratory Corporation of America | RCV000780576 | SCV000917967 | pathogenic | Propionyl-CoA carboxylase deficiency | 2019-09-05 | 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: Five predict the variant abolishes a 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 an individual affected with Propionic Acidemia (Kraus_2012). The same study concluded following cDNA analysis that the allele bearing c.415-2A>C is not transcribed or the mRNA is degraded and found 2% PCC activity in the patient. 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. |