ClinVar Miner

Submissions for variant NM_177438.3(DICER1):c.2191G>A (p.Glu731Lys)

dbSNP: rs869025262
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Paul Sabatier University EA-4555, Paul Sabatier University RCV000207391 SCV000259149 likely benign Anophthalmia-microphthalmia syndrome 2013-01-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000460175 SCV000553644 uncertain significance DICER1-related tumor predisposition 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 731 of the DICER1 protein (p.Glu731Lys). 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: 221950). 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 with a negative predictive value of 80%. 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.
Ambry Genetics RCV001014684 SCV001175424 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-30 criteria provided, single submitter clinical testing The p.E731K variant (also known as c.2191G>A), located in coding exon 13 of the DICER1 gene, results from a G to A substitution at nucleotide position 2191. The glutamic acid at codon 731 is replaced by lysine, 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.
GeneDx RCV003235131 SCV003933661 uncertain significance not provided 2022-12-14 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with sporadic ocular developmental anomalies (ODA) (Chassaing et al., 2016); This variant is associated with the following publications: (PMID: 26893459)
Baylor Genetics RCV003468968 SCV004193452 uncertain significance Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome 2023-06-21 criteria provided, single submitter clinical testing

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