Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000533496 | SCV000626216 | uncertain significance | Fanconi anemia | 2022-10-08 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with serine, which is neutral and polar, at codon 252 of the FANCA protein (p.Asp252Ser). This variant is present in population databases (rs587778324, gnomAD 4%), and has an allele count higher than expected for a pathogenic variant. 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: 134291). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). 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, |
RCV000764091 | SCV000895055 | uncertain significance | Fanconi anemia complementation group A | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| St. |
RCV000533496 | SCV001761648 | uncertain significance | Fanconi anemia | 2021-07-08 | criteria provided, single submitter | clinical testing | The FANCA c.754_755delinsAG (p.Asp252Ser) missense change is absent in gnomAD v2.1.1 (PM2_Supporting; https://gnomad.broadinstitute.org/). 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. |
| Gene |
RCV002272132 | SCV002558576 | uncertain significance | not provided | 2022-01-18 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| St. |
RCV000764091 | SCV004031158 | uncertain significance | Fanconi anemia complementation group A | 2023-08-30 | criteria provided, single submitter | clinical testing | The FANCA c.754_755delinsAG (p.Asp252Ser) change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). In silico tools predict a benign effect of this variant on protein function, but these predictions have not been confirmed by functional studies. 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV002272132 | SCV004218641 | likely benign | not provided | 2023-02-04 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV002272132 | SCV004224297 | uncertain significance | not provided | 2022-12-01 | criteria provided, single submitter | clinical testing | PM2 |
| ITMI | RCV000120964 | SCV000085132 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |