Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003119263 | SCV003790229 | uncertain significance | Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency | 2022-02-23 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 216 of the DNMT3B protein (p.Glu216Gly). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with DNMT3B-related conditions. 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 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. |
| Ambry Genetics | RCV004245944 | SCV004860853 | uncertain significance | Inborn genetic diseases | 2024-01-24 | criteria provided, single submitter | clinical testing | The c.647A>G (p.E216G) alteration is located in exon 6 (coding exon 5) of the DNMT3B gene. This alteration results from a A to G substitution at nucleotide position 647, causing the glutamic acid (E) at amino acid position 216 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |