Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000821572 | SCV000962334 | uncertain significance | Fanconi anemia | 2022-10-23 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with FANCM-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 663651). This variant is present in population databases (rs747356020, gnomAD 0.03%). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1762 of the FANCM protein (p.Pro1762Arg). |
Gene |
RCV002255169 | SCV002526511 | uncertain significance | not provided | 2022-06-15 | 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 |
Fulgent Genetics, |
RCV002501138 | SCV002806810 | uncertain significance | Spermatogenic failure 28; Premature ovarian failure 15 | 2022-01-04 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV002255169 | SCV004218819 | uncertain significance | not provided | 2023-11-04 | criteria provided, single submitter | clinical testing | The FANCM c.5285C>G (p.Pro1762Arg) variant has not been reported in individuals with FANCM-related conditions in the published literature. The frequency of this variant in the general population, 0.00032 (11/34574 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. |
Ambry Genetics | RCV004973014 | SCV005586907 | uncertain significance | Inborn genetic diseases | 2024-11-25 | criteria provided, single submitter | clinical testing | The p.P1762R variant (also known as c.5285C>G), located in coding exon 20 of the FANCM gene, results from a C to G substitution at nucleotide position 5285. The proline at codon 1762 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |