Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000473368 | SCV000547219 | uncertain significance | Fanconi anemia | 2016-11-22 | criteria provided, single submitter | clinical testing | The frequency data for this variant (rs774299094) in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a FANCD2-related disease. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. 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 valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. This sequence change replaces isoleucine with valine at codon 104 of the FANCD2 protein (p.Ile104Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. |
| Fulgent Genetics, |
RCV000764452 | SCV000895514 | uncertain significance | Fanconi anemia complementation group D2 | 2018-10-31 | criteria provided, single submitter | clinical testing |