Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000697468 | SCV000826080 | uncertain significance | Methylmalonic acidemia with homocystinuria, type cblJ | 2021-08-13 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 18 of the ABCD4 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is present in population databases (rs151116417, ExAC 0.006%). Disruption of this splice site has been observed in individual(s) with clinical features of ABCD4-related conditions (Invitae). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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 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. |