Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001059113 | SCV001223722 | uncertain significance | Fanconi anemia | 2022-07-11 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 259 of the FANCA protein (p.Pro259Ala). This variant is present in population databases (rs200988394, gnomAD 0.004%). This missense change has been observed in individual(s) with T-cell acute lymphoblastic leukemia (PMID: 31721781). ClinVar contains an entry for this variant (Variation ID: 854140). 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. Experimental studies have shown that this missense change affects FANCA function (PMID: 31721781). 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 | RCV001800947 | SCV002046912 | uncertain significance | not specified | 2021-04-14 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV001059113 | SCV002535074 | uncertain significance | Fanconi anemia | 2021-04-07 | criteria provided, single submitter | curation | |
St. |
RCV001274648 | SCV005689052 | uncertain significance | Fanconi anemia complementation group A | 2024-08-22 | criteria provided, single submitter | clinical testing | The FANCA c.775C>G (p.Pro259Ala) missense change has a maximum subpopulation frequency of 0.005% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function. To our knowledge, this variant has not been reported in individuals with Fanconi anemia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
Natera, |
RCV001274648 | SCV001459002 | uncertain significance | Fanconi anemia complementation group A | 2020-09-16 | no assertion criteria provided | clinical testing |