ClinVar Miner

Submissions for variant NM_177438.2(DICER1):c.3428T>C (p.Leu1143Pro) (rs139786661)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000205316 SCV000261260 benign DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2020-11-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV000564869 SCV000661830 likely benign Hereditary cancer-predisposing syndrome 2019-05-28 criteria provided, single submitter clinical testing Insufficient evidence
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital RCV000205316 SCV001439188 likely benign DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2020-09-10 criteria provided, single submitter clinical testing The c.3428T>C (p.Leu1143Pro) missense variant has a frequency of 0.0002586 (73 of 282,336 alleles) in gnomAD v2.1.1 with a maximum allele frequency of 0.002904 (72 of 24,794) in the African subpopulation (http://gnomad.broadinstitute.org). This is greater than the expected prevalence of a DICER1 pathogenic variant (BS1, PMID: 24761742). DICER1 has a missense z-score of >3.09 which suggests that this gene has a low rate of benign missense variation and that missense variants are more likely to be damaging (PP2). However, five of seven in silico tools predict a benign effect of this variant on protein function (BP4). This variant has been reported somatically in a case of pediatric acute myeloid leukemia (PMID: 29227476), but to our knowledge, this variant has not been reported in individuals with a personal or family history suggestive of DICER1 Tumor Predisposition syndrome (internal data and literature review). In summary, this variant meets criteria to be classified as likely benign based on the ACMG/AMP criteria: BS1, BP4, PP2.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001289885 SCV001477884 likely benign none provided 2020-03-12 criteria provided, single submitter clinical testing
GeneDx RCV001557273 SCV001779004 likely benign not provided 2021-01-11 criteria provided, single submitter clinical testing

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