Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001879776 | SCV002190640 | uncertain significance | Fanconi anemia | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 628 of the FANCA protein (p.Ala628Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs766422868, ExAC 0.002%). 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: 973639). 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. 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. |
| Ambry Genetics | RCV004035296 | SCV004869457 | uncertain significance | Inborn genetic diseases | 2024-01-09 | criteria provided, single submitter | clinical testing | The c.1882G>A (p.A628T) alteration is located in exon 21 (coding exon 21) of the FANCA gene. This alteration results from a G to A substitution at nucleotide position 1882, causing the alanine (A) at amino acid position 628 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Gene |
RCV004720820 | SCV005327702 | uncertain significance | not provided | 2023-10-06 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| UOSD Laboratory of Genetics & Genomics of Rare Diseases, |
RCV001267761 | SCV001424077 | uncertain significance | Fanconi anemia complementation group A | 2020-05-21 | no assertion criteria provided | clinical testing |