ClinVar Miner

Submissions for variant NM_177438.3(DICER1):c.5171C>T (p.Pro1724Leu)

dbSNP: rs749900564
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen DICER1 and miRNA-Processing Gene Variant Curation Expert Panel, ClinGen RCV001202699 SCV004231824 uncertain significance DICER1-related tumor predisposition 2024-01-09 reviewed by expert panel curation The NM_177438.2: c.5171C>T variant in DICER1 is a missense variant predicted to cause substitution of proline by leucine at amino acid 1724 (p.Pro1724Leu). The highest population minor allele frequency in gnomAD v4.0.0 is 0.00001872 (1/53418 alleles) in European (Finnish) population, followed by 0.00001159 (1/86256 alleles) in South Asian population (PM2_Supporting, BS1, and BA1 are not met). This variant resides within the RNase IIIb mutational hotspot domain with critical functionality as defined by the ClinGen DICER1 VCEP (PM1_Supporting; PMID: 31342592). In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.45; MaxEntScan and SpliceAI: no effect on splicing) (BP4). Due to conflicting evidence, this variant is classified as Uncertain Significance for DICER1-related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: PM1_Supporting, BP4. (Bayesian Points: 0; VCEP specifications version 1.2.0; 01/09/2024)
PreventionGenetics, part of Exact Sciences RCV000851426 SCV000993708 uncertain significance not provided 2016-03-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001202699 SCV001373822 uncertain significance DICER1-related tumor predisposition 2023-06-09 criteria provided, single submitter clinical testing 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 replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1724 of the DICER1 protein (p.Pro1724Leu). ClinVar contains an entry for this variant (Variation ID: 690455). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DICER1 protein function.
Baylor Genetics RCV001202699 SCV001481642 uncertain significance DICER1-related tumor predisposition 2020-01-07 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000851426 SCV002010932 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV002336748 SCV002644984 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-01 criteria provided, single submitter clinical testing The p.P1724L variant (also known as c.5171C>T), located in coding exon 23 of the DICER1 gene, results from a C to T substitution at nucleotide position 5171. The proline at codon 1724 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002495213 SCV002783393 uncertain significance Euthyroid goiter; Rhabdomyosarcoma, embryonal, 2; Pleuropulmonary blastoma; Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome 2022-02-08 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV003321754 SCV004026717 uncertain significance not specified 2023-08-15 criteria provided, single submitter clinical testing

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