ClinVar Miner

Submissions for variant NM_177438.2(DICER1):c.2062C>T (p.Arg688Ter) (rs886037684)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000493794 SCV000581525 pathogenic Hereditary cancer-predisposing syndrome 2015-12-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Donald Williams Parsons Laboratory,Baylor College of Medicine RCV000240958 SCV000599962 pathogenic DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2013-10-28 no assertion criteria provided research This nonsense variant is categorized as deleterious according to ACMG guidelines (PMID:18414213). It was found once in this study maternally inherited in a 1-year-old male with pulmonary pleuroblastoma
GeneDx RCV000384144 SCV000330421 pathogenic not provided 2017-08-23 criteria provided, single submitter clinical testing This variant is denoted DICER1 c.2062C>T at the cDNA level and p.Arg688Ter (R688X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in individuals with pleuropulmonary blastoma, anaplastic sarcoma of the kidney, pineoblastoma, multinodular thyroid disease, and lung and renal cysts (Brenneman 2015, Parsons 2016, Wu 2016, Fita 2017). Based on currently available evidence, we consider this variant to be pathogenic.
International Pleuropulmonary Blastoma Registry,Children's Hospitals and Clinics of Minnesota RCV000240958 SCV000195584 pathogenic DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2014-11-10 criteria provided, single submitter clinical testing
Invitae RCV000240958 SCV000832008 pathogenic DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2018-04-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg688*) in the DICER1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with pleuropulmonary blastoma and nodular hyperplasia (PMID: 26822237, 26925222, 26928971, 28323992),  and has been reported to be de novo in two affected individuals (PMID: 26925222, 28097783). ClinVar contains an entry for this variant (Variation ID: 254303). Loss-of-function variants in DICER1 are known to be pathogenic (PMID: 19556464, 21266384). For these reasons, this variant has been classified as Pathogenic.

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