Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001200786 | SCV003936871 | likely pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2022-09-05 | reviewed by expert panel | curation | The c.1605+2T>A (p.?) variant in ACADVL occurs within the canonical splice donor site (+2) of intron 16. It is predicted to cause skipping of biologically-relevant-exon 16/20, resulting in a frameshift leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124). 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. This variant is absent from gnomAD 2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be 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 ClinGen ACADVL Variant Curation Expert Panel: PVS1, PM2_Supporting (ClinGen ACADVL VCEP specifications version#1; 09-05-2022). |
Wong Mito Lab, |
RCV001200786 | SCV001364984 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2019-11-01 | criteria provided, single submitter | clinical testing | The NM_000018.3:c.1605+2T>A (NP_000009.1:p.?) [GRCH38: NC_000017.11:g.7224395T>A] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: PVS1, PS3 |