ClinVar Miner

Submissions for variant NM_022552.5(DNMT3A):c.875T>C (p.Ile292Thr)

gnomAD frequency: 0.00001  dbSNP: rs777306476
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV001806945 SCV002051618 likely pathogenic not provided 2021-03-05 criteria provided, single submitter clinical testing PS2, PM2, PS3_Moderate, PP3, PP2
GeneDx RCV001806945 SCV002583960 uncertain significance not provided 2025-02-06 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 35904121)
Labcorp Genetics (formerly Invitae), Labcorp RCV002542370 SCV003025889 uncertain significance Tatton-Brown-Rahman overgrowth syndrome 2024-05-16 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 292 of the DNMT3A protein (p.Ile292Thr). This variant is present in population databases (rs777306476, gnomAD 0.002%). This missense change has been observed in individual(s) with Tatton–Brown–Rahman syndrome (PMID: 35904121). ClinVar contains an entry for this variant (Variation ID: 1331601). 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 DNMT3A 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.