Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001231535 | SCV001404061 | uncertain significance | DICER1-related tumor predisposition | 2023-04-11 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 826 of the DICER1 protein (p.Thr826Ala). This variant is not present in population databases (gnomAD no frequency). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DICER1 protein function. ClinVar contains an entry for this variant (Variation ID: 958378). This variant has not been reported in the literature in individuals affected with DICER1-related conditions. |
Ambry Genetics | RCV002447157 | SCV002734618 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-07 | criteria provided, single submitter | clinical testing | The p.T826A variant (also known as c.2476A>G), located in coding exon 15 of the DICER1 gene, results from an A to G substitution at nucleotide position 2476. The threonine at codon 826 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Preventiongenetics, |
RCV003414031 | SCV004106215 | uncertain significance | DICER1-related condition | 2023-09-08 | criteria provided, single submitter | clinical testing | The DICER1 c.2476A>G variant is predicted to result in the amino acid substitution p.Thr826Ala. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant occurs in the RNase IIIb domain, which is a hotspot for missense variants associated with DICER1-related neoplasms (Heravi-Moussavi et al. 2012. PubMed ID: 22187960; Foulkes et al. 2014. PubMed ID: 25176334; Chen et al. 2018. PubMed ID: 31893257). It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/958378/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Baylor Genetics | RCV003469415 | SCV004193491 | uncertain significance | Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome | 2023-05-11 | criteria provided, single submitter | clinical testing |