ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2546G>A (p.Gly849Asp)

gnomAD frequency: 0.00001  dbSNP: rs761130672
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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 RCV000654598 SCV000776492 uncertain significance Multiple endocrine neoplasia, type 2 2024-11-25 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 849 of the RET protein (p.Gly849Asp). This variant is present in population databases (rs761130672, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 543757). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Fulgent Genetics, Fulgent Genetics RCV002485479 SCV002785394 uncertain significance Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A 2022-05-24 criteria provided, single submitter clinical testing
Baylor Genetics RCV004568474 SCV005054235 uncertain significance Hirschsprung disease, susceptibility to, 1 2023-11-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV004948546 SCV005490958 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-28 criteria provided, single submitter clinical testing The p.G849D variant (also known as c.2546G>A), located in coding exon 14 of the RET gene, results from a G to A substitution at nucleotide position 2546. The glycine at codon 849 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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