ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1752-3_1755del

dbSNP: rs2071401309
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen ACADVL Variant Curation Expert Panel, ClinGen 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, Molecular and Human Genetics, Baylor College of Medicine 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

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