Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003453143 | SCV004176827 | likely pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2022-12-14 | reviewed by expert panel | curation | The c.1532+1G>A variant in ACADVL occurs within the canonical splice donor/acceptor site (+/- 1,2) of intron 15. It is predicted to cause skipping of biologically-relevant-exon 15/20, 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). The highest population minor allele frequency in gnomAD v2.1 is 0.000008801 in the European non-Finnish population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (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. (ACADVL VCEP specifications version 1; approved November 8, 2021) |
Eurofins Ntd Llc |
RCV000152740 | SCV000202127 | pathogenic | not provided | 2014-04-14 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV003453143 | SCV004563728 | likely pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2023-08-22 | criteria provided, single submitter | clinical testing | The ACADVL c.1532+1G>A variant (rs727503794), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 166646). This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant disrupts the canonical splice donor site of intron 15, which is likely to negatively impact gene function. Based on available information, this variant is considered to be likely pathogenic. |