Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001041573 | SCV001205197 | uncertain significance | Fanconi anemia | 2023-10-06 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1448 of the FANCM protein (p.Ser1448Phe). This variant is present in population databases (rs774526380, gnomAD 0.003%). 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: 839741). 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 disruptive. 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478671 | SCV004218799 | uncertain significance | not provided | 2023-09-08 | criteria provided, single submitter | clinical testing | In a large-scale breast cancer association study, the variant was observed in individuals with breast cancer (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/FANCM)). The frequency of this variant in the general population, 0.000008 (2/249954 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 conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |