Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001049075 | SCV001213109 | uncertain significance | Perlman syndrome | 2023-04-15 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 747 of the DIS3L2 protein (p.Lys747Arg). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DIS3L2 protein function. ClinVar contains an entry for this variant (Variation ID: 845908). This variant has not been reported in the literature in individuals affected with DIS3L2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.02%). |
| Ambry Genetics | RCV003346279 | SCV004060871 | uncertain significance | Inborn genetic diseases | 2023-08-22 | criteria provided, single submitter | clinical testing | The c.2240A>G (p.K747R) alteration is located in exon 18 (coding exon 17) of the DIS3L2 gene. This alteration results from a A to G substitution at nucleotide position 2240, causing the lysine (K) at amino acid position 747 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |