Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000689316 | SCV000816959 | uncertain significance | Fanconi anemia | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with threonine at codon 517 of the FANCD2 protein (p.Ile517Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
| Illumina Laboratory Services, |
RCV001270757 | SCV001451507 | uncertain significance | Fanconi anemia complementation group D2 | 2019-06-27 | criteria provided, single submitter | clinical testing | The FANCD2 c.1550T>C (p.Ile517Thr) variant is a missense variant. A literature search was performed for the gene, cDNA change and amino acid change. No publications were found based on this search. The variant is reported at a frequency of 0.000009 in the European (non-Finnish) population from the Genome Aggregation Database, though this is based on one allele in a region of good sequencing coverage so the variant is presumed to be rare. Based on the limited evidence, the p.Ile517Thr variant is classified as a variant of uncertain significance for Fanconi anemia. |