ClinVar Miner

Submissions for variant NM_177438.2(DICER1):c.4820G>A (p.Arg1607Gln) (rs368963384)

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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 RCV000570497 SCV000669370 uncertain significance Hereditary cancer-predisposing syndrome 2016-11-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (benign)
Invitae RCV000465086 SCV000553616 uncertain significance DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2018-12-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1607 of the DICER1 protein (p.Arg1607Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs368963384, ExAC 0.03%). This variant has not been reported in the literature in individuals with DICER1-related disease. ClinVar contains an entry for this variant (Variation ID: 412153). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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, 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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