Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000667604 | SCV002538690 | likely pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2022-04-06 | reviewed by expert panel | curation | The c.266del variant in ACADVL is a frameshift predicted to cause a premature stop codon in biologically relevant exon 4/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1: PMIDs 9973285, 11590124). The variant has been identified in at least one individual identified by abnormal newborn screening results suggestive of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency without an additional ACADVL variant identified or follow-up plasma acylcarnitines (PMID: 26385305). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00005437 in East Asian population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). To our knowledge, functional assays have not been reported for this variant. 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 (ACADVL VCEP specifications v2.0; Approved on 12/14/2021). |
Counsyl | RCV000667604 | SCV000792082 | likely pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2017-06-21 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000667604 | SCV000820589 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2023-04-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 552361). This premature translational stop signal has been observed in individual(s) with newborn screening results suggestive of very long chain acyl-coA dehydrogenase deficiency (PMID: 26385305). This variant is present in population databases (rs771808680, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Pro89Hisfs*28) in the ACADVL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACADVL are known to be pathogenic (PMID: 9973285, 11590124). |
Wong Mito Lab, |
RCV000667604 | SCV001364953 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2019-11-01 | criteria provided, single submitter | clinical testing | The NM_000018.3:c.266delC (NP_000009.1:p.Pro89HisfsTer28) [GRCH38: NC_000017.11:g.7220665del] 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 |
Baylor Genetics | RCV000667604 | SCV004216869 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2023-06-24 | criteria provided, single submitter | clinical testing |