Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000458688 | SCV000547761 | uncertain significance | Fanconi anemia | 2024-01-09 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 1061 of the FANCA protein (p.Ser1061Gly). This variant is present in population databases (rs369878171, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with FANCA-related conditions. ClinVar contains an entry for this variant (Variation ID: 408187). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FANCA protein function with a negative predictive value of 80%. 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, |
RCV000765326 | SCV000896586 | uncertain significance | Fanconi anemia complementation group A | 2024-02-06 | criteria provided, single submitter | clinical testing | |
| Genetic Services Laboratory, |
RCV001821266 | SCV002070648 | uncertain significance | not specified | 2019-04-26 | criteria provided, single submitter | clinical testing | |
| Sema4, |
RCV000458688 | SCV002534990 | uncertain significance | Fanconi anemia | 2021-09-07 | criteria provided, single submitter | curation | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477952 | SCV004218549 | uncertain significance | not provided | 2022-08-25 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population, 0.000008 (2/251340 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in patients with adenocarcinoma and small cell lung cancer (PMID: 32107087 (2020)). Additionally, the variant was reported to co-occur with two other pathogenic FANCA variants, in a patient with refractory leukocytopenia and thrombocytopenia (PMID: 31030435 (2019)). 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, |
RCV000765326 | SCV001462886 | uncertain significance | Fanconi anemia complementation group A | 2020-09-16 | no assertion criteria provided | clinical testing |