Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001032358 | SCV001195665 | likely pathogenic | Perlman syndrome | 2022-05-22 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon(s) 15-21 of the DIS3L2 gene, which includes the termination codon. This deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to alter mRNA translation or result in a truncated protein product. This variant has not been reported in the literature in individuals affected with DIS3L2-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant deletes a part of the ribonuclease II domain and all of the S1 RNA-binding domain of the DIS3L2 protein (PMID: 24141620, 23594738, 16957732). While there are no functional studies available for this variant, experimental studies have shown that deletion of S1 RNA-binding domain abolishes DIS3L2 ability to bind and degrade uridylated pre-let-7 RNA (PMID: 23594738). This suggests that disruption of this region of the protein is causative of disease. 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. |