Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000658389 | SCV000780161 | uncertain significance | not provided | 2018-05-30 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the ABCC9 gene. The c.1012-2 A>G variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is also not observed at a significant frequency in large population cohorts (Lek et al., 2016). The c.1012-2 A>G variant destroys the canonical splice acceptor site in intron 6 and is predicted to cause abnormal gene splicing. However, no other splice site variants definitively associated with cardiomyopathy in the ABCC9 gene have been reported in HGMD (Stenson et al., 2014). Additionally, in the absence of functional mRNA studies, the physiological consequence of this variant cannot be precisely determined. |
| Fulgent Genetics, |
RCV002477472 | SCV002778490 | uncertain significance | Hypertrichotic osteochondrodysplasia Cantu type; Dilated cardiomyopathy 1O; Atrial fibrillation, familial, 12; Intellectual disability and myopathy syndrome | 2021-09-04 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002534286 | SCV003456478 | uncertain significance | Dilated cardiomyopathy 1O | 2023-09-29 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 6 of the ABCC9 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 ABCC9 cause disease. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ABCC9-related conditions. ClinVar contains an entry for this variant (Variation ID: 546502). 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. |