Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001988204 | SCV002266032 | uncertain significance | DICER1-related tumor predisposition | 2021-02-15 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with DICER1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with histidine at codon 283 of the DICER1 protein (p.Asp283His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004999585 | SCV005624200 | uncertain significance | not provided | 2024-08-15 | criteria provided, single submitter | clinical testing | The DICER1 c.847G>C (p.Asp283His) variant has not been reported in individuals with DICER1-related conditions in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |