ClinVar Miner

Submissions for variant NM_177438.3(DICER1):c.3093+1G>A

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002857237 SCV003224068 likely pathogenic DICER1-related tumor predisposition 2022-07-29 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with DICER1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 19 of the DICER1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DICER1 are known to be pathogenic (PMID: 19556464, 21266384). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224824 SCV003920878 likely pathogenic Euthyroid goiter; Rhabdomyosarcoma, embryonal, 2; Pleuropulmonary blastoma; Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome 2021-03-30 criteria provided, single submitter clinical testing DICER1 NM_177438.2 exon 19 c.3093+1G>A: This variant has not been reported in the literature and is not present in large control databases. Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant alters the consensus splice sequence (+/- 1,2) which is predicted to result in an absent or abnormal protein. Loss of function variants are a known mechanism of disease for this gene (Slade 2011 PMID:21266384). In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, this variant is classified as likely pathogenic.

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