ClinVar Miner

Submissions for variant NM_177438.3(DICER1):c.2449C>G (p.Pro817Ala)

gnomAD frequency: 0.00001  dbSNP: rs774540239
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001916444 SCV002179886 uncertain significance DICER1-related tumor predisposition 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 817 of the DICER1 protein (p.Pro817Ala). This variant is present in population databases (rs774540239, gnomAD 0.004%). 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: 1410436). 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 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 RCV002449574 SCV002732066 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-19 criteria provided, single submitter clinical testing The p.P817A variant (also known as c.2449C>G), located in coding exon 15 of the DICER1 gene, results from a C to G substitution at nucleotide position 2449. The proline at codon 817 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005006211 SCV005637573 uncertain significance Euthyroid goiter; Rhabdomyosarcoma, embryonal, 2; Pleuropulmonary blastoma; Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome 2024-02-22 criteria provided, single submitter clinical testing

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