ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1605+2T>A

dbSNP: rs1597537351
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen ACADVL Variant Curation Expert Panel, ClinGen 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, Molecular and Human Genetics, Baylor College of Medicine 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
Molecular Genetics, Royal Melbourne Hospital RCV001200786 SCV004812273 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2024-03-01 criteria provided, single submitter clinical testing This sequence change in ACADVL occurs within the canonical splice donor site 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. This variant is absent from the population database gnomAD v4.0. To our knowledge, this variant has not been previously reported in the relevant scientific literature. Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as LIKELY PATHOGENIC. Following criteria are met: PVS1, PM2_Supporting.

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