ClinVar Miner

Submissions for variant NM_177438.2(DICER1):c.4458dup (p.Ser1487fs) (rs1131691197)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000493389 SCV000581536 pathogenic Hereditary cancer-predisposing syndrome 2012-08-27 criteria provided, single submitter clinical testing
GeneDx RCV000657269 SCV000779000 pathogenic not provided 2017-07-25 criteria provided, single submitter clinical testing This duplication of one nucleotide in DICER1 is denoted c.4458dupA at the cDNA level and p.Ser1487IlefsX5 (S1487IfsX5) at the protein level. The normal sequence, with the base that is duplicated in brackets, is CAAAAA[dupA]TCCT. The duplication causes a frameshift which changes a Serine to an Isoleucine at codon 1487, and creates a premature stop codon at position 5 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Invitae RCV000811512 SCV000951780 pathogenic DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2018-12-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1487Ilefs*5) 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 not been reported in the literature in individuals with DICER1-related conditions. ClinVar contains an entry for this variant (Variation ID: 429122). Loss-of-function variants in DICER1 are known to be pathogenic (PMID: 19556464, 21266384). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics RCV000657269 SCV000993757 likely pathogenic not provided 2014-04-17 criteria provided, single submitter clinical testing

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