ClinVar Miner

Submissions for variant NM_177438.3(DICER1):c.3270-1G>C

dbSNP: rs2139972425
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001543117 SCV001761631 pathogenic DICER1-related tumor predisposition 2021-07-22 criteria provided, single submitter clinical testing The DICER1 c.3270-1G>C intronic change results in a G to C substitution at the -1 position of intron 20 of the DICER1 gene (PVS1). Algorithms that predict the impact of sequence changes on splicing indicate that this change may abolish the native splice acceptor site and likely results in an absent or disrupted protein product. This variant is absent in gnomAD v2.1.1 (PM2_supporting; https://gnomad.broadinstitute.org). This variant has been observed in an individual with clinical features of DICER1 syndrome (PS4_supporting; internal data). In summary, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria: PVS1, PS4_supporting, PM2_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001543117 SCV002285821 likely pathogenic DICER1-related tumor predisposition 2021-12-23 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 sequence change affects an acceptor splice site in intron 20 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DICER1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1184717). 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.

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