Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000808664 | SCV000948778 | uncertain significance | Fanconi anemia | 2023-07-31 | criteria provided, single submitter | clinical testing | 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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 652987). This variant has not been reported in the literature in individuals affected with FANCM-related conditions. This variant is present in population databases (rs547223696, gnomAD 0.1%). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 825 of the FANCM protein (p.Ser825Arg). |
Fulgent Genetics, |
RCV002478877 | SCV002787772 | uncertain significance | Spermatogenic failure 28; Premature ovarian failure 15 | 2024-06-19 | criteria provided, single submitter | clinical testing | |
Gene |
RCV003148869 | SCV003837514 | uncertain significance | not provided | 2024-01-16 | 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 |
Ambry Genetics | RCV004028650 | SCV004869905 | uncertain significance | Inborn genetic diseases | 2023-12-13 | criteria provided, single submitter | clinical testing | The c.2473A>C (p.S825R) alteration is located in exon 14 (coding exon 14) of the FANCM gene. This alteration results from a A to C substitution at nucleotide position 2473, causing the serine (S) at amino acid position 825 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003148869 | SCV005626269 | uncertain significance | not provided | 2024-06-10 | criteria provided, single submitter | clinical testing | The FANCM c.2473A>C (p.Ser825Arg) variant has not been reported in individuals with FANCM-related conditions in the published literature. The frequency of this variant in the general population, 0.00097 (33/34024 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. |