Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001038651 | SCV003926503 | uncertain significance | DICER1-related tumor predisposition | 2023-04-25 | reviewed by expert panel | curation | The NM_177438.2:c.5551C>T variant in DICER1 is a missense variant predicted to cause substitution of arginine by cystine at amino acid 1851 (p.Arg1851Cys). This variant is absent from gnomAD v2.1.1 and v3.1.2 (non-cancer) (PM2_Supporting). The computational predictor REVEL gives a score of 0.416, which is below the threshold of 0.5, and the splice site predictors MaxEntScan and SpliceAI indicate that the variant has no impact on splicing, evidence that does not predict a damaging effect on DICER1 function (BP4). In summary, this variant meets the criteria to be classified as Uncertain Significance for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: PM2_Supporting, BP4. (Bayesian Points: 0; VCEP specifications version 1.1.0; 04/25/2023) |
Ambry Genetics | RCV001024265 | SCV001186249 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-21 | criteria provided, single submitter | clinical testing | The p.R1851C variant (also known as c.5551C>T), located in coding exon 25 of the DICER1 gene, results from a C to T substitution at nucleotide position 5551. The arginine at codon 1851 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly 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. |
Invitae | RCV001038651 | SCV001202130 | uncertain significance | DICER1-related tumor predisposition | 2023-05-01 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 825823). This variant has not been reported in the literature in individuals affected with DICER1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1851 of the DICER1 protein (p.Arg1851Cys). |