Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Foulkes Cancer Genetics LDI, |
RCV001201095 | SCV001372119 | pathogenic | DICER1-related tumor predisposition | 2019-07-01 | criteria provided, single submitter | curation | ACMG criteria met: PS2, PS3, PM1, PM2, PP4 |
Labcorp Genetics |
RCV001201095 | SCV003010466 | uncertain significance | DICER1-related tumor predisposition | 2022-04-15 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 1810 of the DICER1 protein (p.Asp1810Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed as a mosaic variant in an individual with pleuropulmonary blastoma, a Sertoli-Leydig cell tumor, and cystic nephroma (PMID: 26925222). ClinVar contains an entry for this variant (Variation ID: 933084). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Studies have shown that this missense change is associated with altered splicing resulting in unknown protein product impact (PMID: 26545620). 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. |