Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001200789 | SCV004176831 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2022-12-14 | reviewed by expert panel | curation | The c.1752-3_1755del variant in ACADVL deletes the canonical splice acceptor site (- 1,2) of intron 18. It is predicted to cause skipping of biologically-relevant-exon 19/20, resulting in a frameshift leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID 9973285, 11590124). At least one patient with this variant displayed increased acylcarnitines, which is highly specific for very long chain acyl-CoA dehydrogenase (VLCAD) deficiency. (PP4, PMID: 30626930). Additionally, at least two individuals with this variant were identified by newborn screen, but this information is insufficient to use toward classification (PMID: 26385305, 35281663). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as pathogenic for autosomal recessive VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PVS1, PP4, PM2_Supporting (ACADVL VCEP specifications version 1; approved November 8, 2021). |
Wong Mito Lab, |
RCV001200789 | SCV001364988 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2019-11-01 | criteria provided, single submitter | clinical testing | The NM_000018.3:c.1752-3_1755del7 (NP_000009.1:p.?) [GRCH38: NC_000017.11:g.7224806_7224812del] 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 |