Description
The c.1606-3_1606-2del variant in ACADVL is a variant that causes a deletion in the canonical splice acceptor site of intron 17. RNA studies in patient cells carrying this variant show that this variant causes use of a cryptic acceptor and deletion of 4 nucleotides of the transcript (P3_Supporting; PMID: 11914034). This is predicted to result 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). This variant has been reported in trans to a pathogenic variant in an affected individual (PM3; PMID: 11914034). In cells derived from this individual, VLCAD enzyme activity was less than 20% of controls, which is highly specific for very long chain acyl-CoA dehydrogenase (VLCAD) deficiency (PP4_Moderate). 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, PM3, PP4_Moderate, PM2_Supporting, PS3_Supporting (ACADVL VCEP specifications version 1; approved November 8, 2021).
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
