Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001052315 | SCV001216520 | likely pathogenic | not provided | 2023-11-20 | criteria provided, single submitter | clinical testing | This variant results in the deletion of part of exon 2 (c.151-1_151del) of the ACAD9 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ACAD9 are known to be pathogenic (PMID: 25721401). This variant is present in population databases (rs766026673, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ACAD9-related conditions. ClinVar contains an entry for this variant (Variation ID: 848539). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282438 | SCV002570854 | likely pathogenic | Mitochondrial complex I deficiency | 2022-07-14 | criteria provided, single submitter | clinical testing | Variant summary: ACAD9 c.151-1_151delGA is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a canonical 3 acceptor site and creates a new cryptic exonic one, resulting in the deletion of part of exon 2. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 249802 control chromosomes (gnomAD). To our knowledge, no occurrence of c.151-1_151delGA in individuals affected with Mitochondrial Complex I Deficiency, Nuclear Type 20 and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Baylor Genetics | RCV001275863 | SCV004207030 | likely pathogenic | Acyl-CoA dehydrogenase 9 deficiency | 2023-10-31 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001275863 | SCV001461495 | likely pathogenic | Acyl-CoA dehydrogenase 9 deficiency | 2020-09-16 | no assertion criteria provided | clinical testing |