Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000818486 | SCV000959101 | uncertain significance | Fanconi anemia | 2022-10-26 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1950 of the FANCM protein (p.Leu1950Val). This variant is present in population databases (rs146436929, gnomAD 0.07%). This missense change has been observed in individual(s) with Fanconi anemia (PMID: 26740942). ClinVar contains an entry for this variant (Variation ID: 661134). 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: "Probably 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. |
Gene |
RCV001731943 | SCV001982904 | uncertain significance | not provided | 2023-10-06 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26740942) |
Fulgent Genetics, |
RCV002507433 | SCV002816289 | uncertain significance | Spermatogenic failure 28; Premature ovarian failure 15 | 2022-03-16 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001731943 | SCV004218832 | uncertain significance | not provided | 2023-06-19 | criteria provided, single submitter | clinical testing | In the published literature, this variant has been reported in an individual with Fanconi anemia (PMID: 26740942 (2015)). The frequency of this variant in the general population, 0.00072 (18/24972 chromosomes in African/African 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 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. |
Mendelics | RCV003492178 | SCV004232593 | likely benign | Hereditary cancer | 2024-01-23 | criteria provided, single submitter | clinical testing |