Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001067604 | SCV001232672 | uncertain significance | Fanconi anemia | 2024-08-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1265 of the FANCM protein (p.Glu1265Gly). This variant is present in population databases (rs763808637, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with FANCM-related conditions. ClinVar contains an entry for this variant (Variation ID: 861151). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
| Baylor Genetics | RCV001292736 | SCV001481368 | uncertain significance | Spermatogenic failure 28 | 2020-08-27 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Gene |
RCV004726862 | SCV005333271 | uncertain significance | not provided | 2024-03-01 | criteria provided, single submitter | clinical testing | 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 |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004726862 | SCV005626292 | uncertain significance | not provided | 2024-03-29 | criteria provided, single submitter | clinical testing | The FANCM c.3794A>G (p.Glu1265Gly) variant has not been reported in individuals with FANCM-related conditions in the published literature. The frequency of this variant in the general population, 0.00046 (15/32870 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. |