Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000694134 | SCV000822565 | uncertain significance | Fanconi anemia | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 1832 of the FANCM protein (p.Glu1832Asp). This variant is present in population databases (rs374303319, gnomAD 0.02%). 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: 572693). 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. |
Gene |
RCV002473114 | SCV002770278 | uncertain significance | not provided | 2023-07-14 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with stomach adenocarcinoma (Lu et al., 2015); This variant is associated with the following publications: (PMID: 26689913) |
Fulgent Genetics, |
RCV002477573 | SCV002776459 | uncertain significance | Spermatogenic failure 28; Premature ovarian failure 15 | 2021-12-15 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV002473114 | SCV004218823 | uncertain significance | not provided | 2023-06-28 | criteria provided, single submitter | clinical testing | This variant has not been reported in the published literature. The frequency of this variant in the general population, 0.00016 (3/18388 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. |
Prevention |
RCV004737956 | SCV005367444 | uncertain significance | FANCM-related disorder | 2024-08-13 | no assertion criteria provided | clinical testing | The FANCM c.5496A>C variant is predicted to result in the amino acid substitution p.Glu1832Asp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.016% of alleles in individuals of East Asian descent in gnomAD and has been interpreted as variant of uncertain significance in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/572693/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |