ClinVar Miner

Submissions for variant NM_177438.3(DICER1):c.1631G>A (p.Arg544Gln)

gnomAD frequency: 0.00001  dbSNP: rs143533680
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000528971 SCV000658133 uncertain significance DICER1-related tumor predisposition 2023-10-06 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 544 of the DICER1 protein (p.Arg544Gln). This variant is present in population databases (rs143533680, gnomAD 0.01%). 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: 477049). 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. 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 RCV001012501 SCV001172961 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-01 criteria provided, single submitter clinical testing The c.1631G>A (p.R544Q) alteration is located in exon 10 (coding exon 9) of the DICER1 gene. This alteration results from a G to A substitution at nucleotide position 1631, causing the arginine (R) at amino acid position 544 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Illumina Laboratory Services, Illumina RCV000528971 SCV001274683 benign DICER1-related tumor predisposition 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Baylor Genetics RCV003470770 SCV004193383 uncertain significance Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome 2023-09-02 criteria provided, single submitter clinical testing

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