Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001321190 | SCV001512009 | uncertain significance | Fanconi anemia | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 1299 of the FANCD2 protein (p.Arg1299His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs781701459, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with FANCD2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
| Fulgent Genetics, |
RCV002499625 | SCV002814936 | uncertain significance | Fanconi anemia complementation group D2 | 2022-03-12 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002546083 | SCV003576664 | uncertain significance | Inborn genetic diseases | 2021-09-27 | criteria provided, single submitter | clinical testing | The c.3896G>A (p.R1299H) alteration is located in exon 40 (coding exon 39) of the FANCD2 gene. This alteration results from a G to A substitution at nucleotide position 3896, causing the arginine (R) at amino acid position 1299 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |