Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| St. |
RCV001554281 | SCV001775510 | uncertain significance | Fanconi anemia | 2021-07-29 | criteria provided, single submitter | clinical testing | The FANCA c.876C>G (p.His292Gln) missense change has a maximum subpopulation frequency of 0.0050% in gnomAD v2.1.1 (PM2_supporting; https://gnomad.broadinstitute.org/variant/16-89865591-G-C). Seven of seven in silico tools predict a benign effect of this variant on protein function (BP4), but to our knowledge these predictions have not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Fanconi anemia. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2_Supporting, BP4. |
| Labcorp Genetics |
RCV001554281 | SCV003499702 | uncertain significance | Fanconi anemia | 2022-07-02 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 292 of the FANCA protein (p.His292Gln). This variant is present in population databases (rs527897404, 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: 1192512). 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. |