Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002286572 | SCV002576782 | likely pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2022-12-14 | reviewed by expert panel | curation | The c.316_325del (p.Val106Cysfs*8) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 5/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs: 9973285, 11590124). This variant is absent from gnomAD 2.1.1 (PM2_Supporting). To our knowledge, this variant has not been reported in the literature in any individuals with VLCADD. To our knowledge, functional assays have not been reported for this variant. In summary, this variant has been classified as LIKELY PATHOGENIC for autosomal recessive very long chain acyl-CoA dehydrogenase (VLCAD) deficiency based on the ACMG/AMP criteria applied, as specified by the ACADVL Expert Panel: PVS1, PM2_Supporting (ClinGen ACADVL VCEP specifications version#2.0; approved 05-09-22). |
Gene |
RCV000412713 | SCV000492224 | pathogenic | not provided | 2016-11-22 | criteria provided, single submitter | clinical testing | The c.316_325del10 variant in the ACADVL gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.316_325del10 variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.316_325del10 variant causes a frameshift starting with codon Valine 106, changes this amino acid to a Cysteine residue and creates a premature Stop codon at position 8 of the new reading frame, denoted p.Val106CysfsX8. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret c.316_325del10 to be pathogenic. |