Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001214821 | SCV001386526 | uncertain significance | Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency | 2022-06-01 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 395 of the DNMT3B protein (p.Ala395Thr). This variant is present in population databases (rs753291521, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with DNMT3B-related conditions. ClinVar contains an entry for this variant (Variation ID: 944424). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |