Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001366149 | SCV001562443 | uncertain significance | Fanconi anemia | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 948 of the FANCA protein (p.Asp948His). This variant is present in population databases (rs778254482, gnomAD 0.004%). 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: 1057210). 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 expected to disrupt FANCA 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. |
Sema4, |
RCV001366149 | SCV002534973 | uncertain significance | Fanconi anemia | 2022-03-17 | criteria provided, single submitter | curation | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478797 | SCV004221983 | uncertain significance | not provided | 2023-07-04 | criteria provided, single submitter | clinical testing | This variant has not been reported in the published literature. The frequency of this variant in the general population, 0.0000071 (2/282876 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the 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 conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
Ambry Genetics | RCV004036964 | SCV004869461 | uncertain significance | Inborn genetic diseases | 2024-01-04 | criteria provided, single submitter | clinical testing | The c.2842G>C (p.D948H) alteration is located in exon 29 (coding exon 29) of the FANCA gene. This alteration results from a G to C substitution at nucleotide position 2842, causing the aspartic acid (D) at amino acid position 948 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001366149 | SCV002092575 | uncertain significance | Fanconi anemia | 2020-01-17 | no assertion criteria provided | clinical testing |