Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477171 | SCV004221810 | uncertain significance | not provided | 2022-09-28 | criteria provided, single submitter | clinical testing | This variant has not been described in online databases. The frequency of this variant in the general population, 0.000004 (1/251354 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual with non-small cell lung cancer (PMID: 31417090 (2019)). 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. Additional analysis using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant may affect proper DICER1 mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant. |
| Labcorp Genetics |
RCV003588928 | SCV004276832 | uncertain significance | DICER1-related tumor predisposition | 2023-04-14 | 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. This variant has not been reported in the literature in individuals affected with DICER1-related conditions. This variant is present in population databases (rs757277030, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 935 of the DICER1 protein (p.Arg935Lys). This variant also falls at the last nucleotide of exon 17, which is part of the consensus splice site for this exon. |