ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.1072G>A (p.Glu358Lys)

gnomAD frequency: 0.00001  dbSNP: rs746643140
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003237679 SCV002011504 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001861124 SCV002252976 uncertain significance Fanconi anemia 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 358 of the FANCM protein (p.Glu358Lys). This variant is present in population databases (rs746643140, gnomAD 0.0009%). 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: 1319689). 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.
GeneDx RCV003237679 SCV004168213 uncertain significance not provided 2023-04-19 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003237679 SCV004218705 uncertain significance not provided 2023-03-09 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.000004 (1/251324 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In a breast cancer association study, the variant was observed in a breast cancer case (see LOVD (http://databases.lovd.nl/shared/genes/FANCM) and PMID: 33471991 (2021)). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.