ClinVar Miner

Submissions for variant NM_177438.2(DICER1):c.5103C>G (p.Tyr1701Ter) (rs875989780)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000627364 SCV000748357 pathogenic not provided 2018-04-27 criteria provided, single submitter clinical testing The Y1701X variant in the DICER1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. However, a different nucleotide substitution (c.5103 C>A) resulting in the Y1701X variant has been reported previously in an individual with a pineoblastoma (de Kock et al., 2014). The Y1701X variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Y1701X variant is not observed in large population cohorts (Lek et al., 2016). We interpret Y1701X as a pathogenic variant.
Invitae RCV000654463 SCV000776357 pathogenic DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2017-12-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr1701*) 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 reported in an individual affected with pineoblastoma and thyroid nodule. In addition, absence of DICER1 immunostaining within this individual's tumors was detected (PMID: 25022261). 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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