Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV000809781 | SCV002599116 | uncertain significance | DICER1-related tumor predisposition | 2024-10-22 | reviewed by expert panel | curation | The NM_177438.3:c.5656G>A variant in DICER1 is a missense variant predicted to cause substitution of glycine by arginine at amino acid 1886. This variant has an allele frequency of 0.000000847 (1/1180038 alleles) across gnomAD v4.1.0 with no more than one allele in any subpopulation, which is lower than the ClinGen DICER1 VCEP threshold (<0.000005) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). The computational predictor REVEL gives a score of 0.572 which is neither above nor below the thresholds predicting a damaging or benign impact on DICER1 function (PP3 and BP4 not met). In summary, this variant meets the criteria to be classified as a Uncertain Significance for DICER1-related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 and miRNA-Processing Gene VCEP: PM2_Supporting (Bayesian Points: 1, VCEP specifications version 1.3.0; 10/22/2024). |
| Labcorp Genetics |
RCV000809781 | SCV000949956 | uncertain significance | DICER1-related tumor predisposition | 2022-03-10 | 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 653922). This missense change has been observed in individual(s) with Wilms tumor (PMID: 25670083). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1886 of the DICER1 protein (p.Gly1886Arg). |
| Foulkes Cancer Genetics LDI, |
RCV000809781 | SCV001372211 | likely pathogenic | DICER1-related tumor predisposition | 2019-07-01 | criteria provided, single submitter | curation | ACMG criteria met: PS1, PM1, PM2, BP1 |
| Ambry Genetics | RCV004609539 | SCV005110911 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-25 | criteria provided, single submitter | clinical testing | The p.G1886R variant (also known as c.5656G>A), located in coding exon 26 of the DICER1 gene, results from a G to A substitution at nucleotide position 5656. The glycine at codon 1886 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |