ClinVar Miner

Submissions for variant NM_177438.2(DICER1):c.662A>T (p.Glu221Val) (rs757925350)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569381 SCV000669444 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000814385 SCV000954793 uncertain significance DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2018-11-06 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with valine at codon 221 of the DICER1 protein (p.Glu221Val). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and valine. This variant is present in population databases (rs757925350, ExAC 0.01%). This variant has not been reported in the literature in individuals with DICER1-related disease. ClinVar contains an entry for this variant (Variation ID: 483472). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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, 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.

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