Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001854948 | SCV002769754 | likely benign | Very long chain acyl-CoA dehydrogenase deficiency | 2022-12-14 | reviewed by expert panel | curation | The c.1533G>A (p.Arg511=) variant is a synonymous (silent) variant that is not predicted by (SpliceAI, MaxEntScn, NNSplice) to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by the 100 vertebrate Basewise Conservation by PhyloP track in the UCSC genome browser (BP4, BP7). This variant is absent from gnomAD v2.1.1; however, this is not considered conflicting evidence with BP4 and BP7. In summary, this variant meets the criteria to be classified as likely benign 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: BP4, BP7 (ACADVL VCEP specifications version 1; approved November 8, 2021) |
Prevention |
RCV000250784 | SCV000301516 | benign | not specified | criteria provided, single submitter | clinical testing | ||
Invitae | RCV001854948 | SCV002277686 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2022-06-27 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 254695). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. This variant has not been reported in the literature in individuals affected with ACADVL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 511 of the ACADVL mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ACADVL protein. It affects a nucleotide within the consensus splice site. |