Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001222318 | SCV001394412 | uncertain significance | Fanconi anemia | 2021-10-21 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with valine at codon 582 of the FANCD2 protein (p.Ala582Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs768105189, ExAC 0.01%). 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 valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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, |
RCV001270809 | SCV001451573 | uncertain significance | Fanconi anemia complementation group D2 | 2019-06-27 | criteria provided, single submitter | clinical testing | The FANCD2 c.1745C>T (p.Ala582Val) 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 0.000131 in the South Asian population of the Genome Aggregation Database. Based on the limited evidence, the p.Ala582Val variant is classified as a variant of uncertain significance for Fanconi anemia. |