Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 3billion | RCV002250944 | SCV002521183 | pathogenic | Congenital bile acid synthesis defect 6 | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Invitae | RCV003774731 | SCV004620795 | uncertain significance | not provided | 2024-01-06 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 3 of the ACOX2 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), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ACOX2 cause disease. This variant is present in population databases (rs751041263, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with bile acid synthesis defect (PMID: 35775617). ClinVar contains an entry for this variant (Variation ID: 1687262). 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. |