ClinVar Miner

Submissions for variant NM_177438.3(DICER1):c.1410G>C (p.Glu470Asp)

gnomAD frequency: 0.00004  dbSNP: rs774271782
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000559384 SCV000658121 uncertain significance DICER1-related tumor predisposition 2025-01-29 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 470 of the DICER1 protein (p.Glu470Asp). This variant is present in population databases (rs774271782, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with DICER1-related conditions. ClinVar contains an entry for this variant (Variation ID: 477037). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt DICER1 protein function with a negative predictive value of 95%. 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.
Ambry Genetics RCV001011407 SCV001171724 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-20 criteria provided, single submitter clinical testing The p.E470D variant (also known as c.1410G>C), located in coding exon 8 of the DICER1 gene, results from a G to C substitution at nucleotide position 1410. The glutamic acid at codon 470 is replaced by aspartic acid, an amino acid with highly similar 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV003325204 SCV004031150 uncertain significance Pleuropulmonary blastoma 2023-08-30 criteria provided, single submitter clinical testing The DICER1 c.1410G>C (p.Glu470Asp) missense change is absent in gnomAD non-cancer v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function and no splicing effects are predicted, but to our knowledge these predictions have not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with DICER1-associated tumors. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
PreventionGenetics, part of Exact Sciences RCV003403339 SCV004121421 uncertain significance DICER1-related disorder 2023-03-19 criteria provided, single submitter clinical testing The DICER1 c.1410G>C variant is predicted to result in the amino acid substitution p.Glu470Asp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/14-95584058-C-G) and is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/477037/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV003470768 SCV004193443 uncertain significance Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome 2023-06-30 criteria provided, single submitter clinical testing
GeneDx RCV004767385 SCV005376340 uncertain significance not provided 2023-10-16 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function

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