Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000493694 | SCV000583243 | likely pathogenic | not provided | 2016-09-15 | criteria provided, single submitter | clinical testing | The c.2545+5 G>C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.2545+5 G>C variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved across species. Several in-silico splice prediction models predict that c.2545+5 G>C destroys the natural splice donor site in intron 22. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this fetus is unknown. Although this variant has not been previously reported to our knowledge, another splice site variant at the same position has been reported in association with tuberous sclerosis (TSC2 LOVD). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| Fulgent Genetics, |
RCV000763366 | SCV000894062 | likely pathogenic | Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2 | 2018-10-31 | criteria provided, single submitter | clinical testing |