Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001042756 | SCV001206457 | uncertain significance | DICER1-related tumor predisposition | 2022-01-28 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 840696). This variant has not been reported in the literature in individuals affected with DICER1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1922 of the DICER1 protein (p.Ser1922Asn). |
| Ambry Genetics | RCV002355004 | SCV002651732 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-01 | criteria provided, single submitter | clinical testing | The p.S1922N variant (also known as c.5765G>A), located in coding exon 26 of the DICER1 gene, results from a G to A substitution at nucleotide position 5765. The serine at codon 1922 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |