ClinVar Miner

Submissions for variant NM_177438.2(DICER1):c.5516G>A (p.Arg1839Gln) (rs587778233)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000566657 SCV000669355 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
ITMI RCV000120645 SCV000084806 not provided not specified 2013-09-19 no assertion provided reference population
Invitae RCV000476806 SCV000553543 uncertain significance DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2018-12-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1839 of the DICER1 protein (p.Arg1839Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs587778233, ExAC 0.006%). This variant has not been reported in the literature in individuals with DICER1-related disease. ClinVar contains an entry for this variant (Variation ID: 133976). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant has uncertain impact on DICER1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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