ClinVar Miner

Submissions for variant NM_177438.2(DICER1):c.3540C>A (p.Tyr1180Ter) (rs886037704)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Pleuropulmonary Blastoma Registry,Children's Hospitals and Clinics of Minnesota RCV000240887 SCV000195605 pathogenic DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2014-11-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV000494658 SCV000581535 pathogenic Hereditary cancer-predisposing syndrome 2017-11-09 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)
GeneDx RCV000627259 SCV000748251 pathogenic not provided 2018-03-12 criteria provided, single submitter clinical testing The Y1180X variant in the DICER1 gene has been reported previously in a family with pleuropulmonary blastoma, and in an individual with ovarian Sertoli-Leydig tumor, fetal adenocarcinoma of the lung, and familial multinodular goiter (Hill et al., 2009; Brenneman et al., 2015; Wu et al., 2014). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Y1180X variant is not observed in large population cohorts (Lek et al., 2016). We interpret Y1180X as a pathogenic variant.
Invitae RCV000240887 SCV000938511 pathogenic DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2018-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr1180*) 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 an individual affected with pleuropulmonary blastoma (PMID: 19556464) and an individual affected with ovarian Sertoli-Leydig cell tumor, fetal adenocarcinoma of the lung, and multinodular goiter (PMID: 25451712, 26886166). This variant is also known as c.3722C>A (Y1170*) in the literature. ClinVar contains an entry for this variant (Variation ID: 254323). 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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