ClinVar Miner

Submissions for variant NM_177438.3(DICER1):c.3007C>T (p.Arg1003Ter)

dbSNP: rs1060503605
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000465236 SCV000553533 pathogenic DICER1-related tumor predisposition 2024-06-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1003*) in the DICER1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DICER1 are known to be pathogenic (PMID: 19556464, 21266384). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with pleuropulmonary blastoma (PMID: 24675358). ClinVar contains an entry for this variant (Variation ID: 412077). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV000851456 SCV000993740 pathogenic not provided 2017-08-23 criteria provided, single submitter clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000465236 SCV001372156 pathogenic DICER1-related tumor predisposition 2019-07-01 criteria provided, single submitter curation ACMG criteria met: PVS1, PM2, PP4
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV003230265 SCV003928065 pathogenic Pleuropulmonary blastoma 2023-03-27 criteria provided, single submitter clinical testing The DICER1 c.3007C>T (p.Arg1003Ter) change is a nonsense variant that is predicted to cause premature protein truncation or absence of protein due to nonsense-mediated decay. This variant has been reported in multiple individuals with DICER1 syndrome (PMID: 35728810, 32729194, 28459098, internal data), including at least one individual whose tumor harbored a second pathogenic variant in the DICER1 gene. In summary, this variant meets criteria to be classified as pathogenic.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV003230265 SCV004808045 pathogenic Pleuropulmonary blastoma 2024-03-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV004948335 SCV005566160 pathogenic Hereditary cancer-predisposing syndrome 2024-11-12 criteria provided, single submitter clinical testing The p.R1003* pathogenic mutation (also known as c.3007C>T), located in coding exon 18 of the DICER1 gene, results from a C to T substitution at nucleotide position 3007. This changes the amino acid from an arginine to a stop codon within coding exon 18. This alteration was identified in multiple individuals diagnosed with sarcoma (Mullen MM et al. Gynecol Oncol Rep, 2017 May;20:121-124; Schweizer L et al. Neuropathol Appl Neurobiol, 2022 Oct;48:e12830). This alteration was also identified in an individual diagnosed with a Sertoli-Leydig cell tumor (Koo J et al. Pediatr Blood Cancer, 2020 Oct;67:e28621). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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