ClinVar Miner

Submissions for variant NM_177438.2(DICER1):c.2247C>A (p.Tyr749Ter) (rs886037689)

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Total submissions: 3
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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 RCV000240935 SCV000195589 pathogenic DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2014-11-10 criteria provided, single submitter clinical testing
GeneDx RCV000480985 SCV000568868 pathogenic not provided 2017-11-17 criteria provided, single submitter clinical testing This variant is denoted DICER1 c.2247C>A at the cDNA level and p.Tyr749Ter (Y749X) at the protein level. The substitution creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAC>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. DICER1 Tyr749Ter segregated with disease in a large family with DICER1-Pleuropulmonary Blastoma Familial Tumor Predisposition Syndrome, and lymphoblasts from carriers of this variant showed reduction of the variant mRNA (Hill 2009). DICER1 Tyr749Ter has also been reported in at least two other individuals with personal and family histories of DICER1-related tumors (Doros 2012, Brenneman 2015). This variant is considered pathogenic.
Ambry Genetics RCV000493504 SCV000581605 pathogenic Hereditary cancer-predisposing syndrome 2013-03-26 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)

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