Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000704355 | SCV000833300 | uncertain significance | Fanconi anemia | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with cysteine at codon 488 of the FANCA protein (p.Tyr488Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with FANCA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The cysteine 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478440 | SCV004221923 | uncertain significance | not provided | 2022-10-18 | criteria provided, single submitter | clinical testing | The variant has not been reported in the published literature. The frequency of this variant in the general population, 0.0000071 (2/282788 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
Natera, |
RCV001274148 | SCV001457952 | uncertain significance | Fanconi anemia complementation group A | 2020-09-16 | no assertion criteria provided | clinical testing |