Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV004702449 | SCV005205569 | likely benign | Hereditary cancer | 2024-09-11 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following: it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease, and/or has normal protein function, and/or has lack of segregation with disease, and/or has been detected in co-occurrence with known pathogenic variant, and/or has lack of disease association in case-control studies, and/or is located in a region inconsistent with a known cause of pathogenicity. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV002307626 | SCV004218812 | uncertain significance | not provided | 2023-12-01 | criteria provided, single submitter | clinical testing | The FANCM c.4934G>A (p.Arg1645His) variant has been reported in the published literature in individuals with breast cancer as (PMIDs: 29351780 (2018), 33471991 (2021), 36707629 (2023)), see also LOVD (http://databases.lovd.nl/shared/genes/FANCM)) and ovarian cancer (PMID: 28881617 (2017)). In addition, this variant has been reported in unaffected individuals (PMID: 33471991 (2021), 36707629 (2023)), see also LOVD (http://databases.lovd.nl/shared/genes/FANCM)). The frequency of this variant in the general population, 0.0002 (5/24908 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. |
| Revvity Omics, |
RCV002307626 | SCV003833941 | uncertain significance | not provided | 2019-11-19 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002487794 | SCV002787434 | uncertain significance | Spermatogenic failure 28; Premature ovarian failure 15 | 2024-06-08 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002307626 | SCV002601275 | uncertain significance | not provided | 2025-02-19 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 36707629, 29351780, 33471991) |
| Labcorp Genetics |
RCV000815706 | SCV000956172 | uncertain significance | Fanconi anemia | 2026-02-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1645 of the FANCM protein (p.Arg1645His). This variant is present in population databases (rs377502779, gnomAD 0.02%). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 29351780). ClinVar contains an entry for this variant (Variation ID: 658816). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The histidine 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. |