Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000809258 | SCV000949401 | uncertain significance | Fanconi anemia | 2022-10-26 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 398 of the FANCM protein (p.Arg398Gln). This variant is present in population databases (rs530233908, gnomAD 0.1%). This missense change has been observed in individual(s) with male breast cancer (PMID: 30613976). ClinVar contains an entry for this variant (Variation ID: 653476). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
Sema4, |
RCV002259023 | SCV002527308 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-25 | criteria provided, single submitter | curation | |
Gene |
RCV003151815 | SCV003840688 | uncertain significance | not provided | 2023-09-26 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with breast cancer (Rizzolo et al., 2019); This variant is associated with the following publications: (PMID: 33471991, 30613976) |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003151815 | SCV004218710 | uncertain significance | not provided | 2023-08-22 | criteria provided, single submitter | clinical testing | In the published literature, this variant has been reported in individuals with breast cancer (PMID: 30613976 (2019), 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/FANCM)). This variant has also been reported in unaffected individuals (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/FANCM)). The frequency of this variant in the general population, 0.0011 (38/34912 chromosomes in Latino/Admixed American subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. 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. |