Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001571997 | SCV001796567 | uncertain significance | not provided | 2023-05-04 | criteria provided, single submitter | clinical testing | Not observed at a 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 |
Labcorp Genetics |
RCV001866036 | SCV002202734 | uncertain significance | Fanconi anemia | 2023-03-24 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 40 of the FANCM protein (p.Ala40Gly). This variant is present in population databases (rs750184645, gnomAD 0.003%). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1205354). This variant has not been reported in the literature in individuals affected with FANCM-related conditions. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001571997 | SCV005626240 | uncertain significance | not provided | 2024-07-03 | criteria provided, single submitter | clinical testing | The FANCM c.119C>G (p.Ala40Gly) variant has been reported in the published literature in an individual affected with ovarian cancer as well as reportedly healthy individual (PMID: 28881617 (2017)). The frequency of this variant in the general population, 0.000026 (3/113588 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 predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |