ClinVar Miner

Submissions for variant NM_177438.3(DICER1):c.2830C>T (p.Arg944Ter)

dbSNP: rs137852978
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Pleuropulmonary Blastoma Registry, Children's Hospitals and Clinics of Minnesota RCV000240862 SCV000195593 pathogenic DICER1-related tumor predisposition 2014-11-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV000493701 SCV000581602 pathogenic Hereditary cancer-predisposing syndrome 2020-06-25 criteria provided, single submitter clinical testing The p.R944* pathogenic mutation (also known as c.2830C>T), located in coding exon 17 of the DICER1 gene, results from a C to T substitution at nucleotide position 2830. This changes the amino acid from an arginine to a stop codon within coding exon 17. Designated as 3012C>T (R934X), this mutation was seen in a family with pleuropulmonary blastoma (Hill DA et al. Science 2009 Aug;325:965). It was identified in a patient diagnosed with pleuropulmonary blastoma at three years of age, as well as in her mother, who had bilateral ovarian Sertoli-Leydig cell tumors and papillary thyroid carcinoma (Puckett Y et al. J Pediatr Surg Case Rep 2015 Aug;3:8). This alteration was also identified in a woman with a right duplicated collecting system, simple 8 mm outer cortex, and renal cyst/s (Khan NE et al. Pediatr. Nephrol. 2018 Dec;33:2281-2288). 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.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000240862 SCV001372081 pathogenic DICER1-related tumor predisposition 2019-07-01 criteria provided, single submitter curation ACMG criteria met: PVS1, PM2, PP4
Labcorp Genetics (formerly Invitae), Labcorp RCV000240862 SCV001592669 pathogenic DICER1-related tumor predisposition 2022-07-04 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 4470). This variant is also known as 3012C>T R934X. This premature translational stop signal has been observed in individual(s) with clinical features of DICER1-related pleuropulmonary blastoma familial tumor predisposition syndrome (PMID: 19556464, 26925222, 28323992, 30178239). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg944*) 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).
GeneDx RCV004719622 SCV005325239 pathogenic not provided 2024-03-11 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 19556464, 34008223, 28323992, Pukett_2015, 30178239)
OMIM RCV000004727 SCV000024903 pathogenic Pleuropulmonary blastoma 2009-08-21 no assertion criteria provided literature only

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