ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.5440G>A (p.Glu1814Lys)

gnomAD frequency: 0.00013  dbSNP: rs139074680
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000989214 SCV001139443 uncertain significance Fanconi anemia complementation group A 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001061433 SCV001226176 uncertain significance Fanconi anemia 2023-12-30 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 1814 of the FANCM protein (p.Glu1814Lys). This variant is present in population databases (rs139074680, gnomAD 0.04%). 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: 803023). 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 lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV001593165 SCV001826476 uncertain significance not provided 2024-03-13 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
Breakthrough Genomics, Breakthrough Genomics RCV001593165 SCV005191360 uncertain significance not provided criteria provided, single submitter not provided
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001593165 SCV005626328 uncertain significance not provided 2024-02-15 criteria provided, single submitter clinical testing The FANCM c.5440G>A (p.Glu1814Lys) variant has been observed in the published literature in individuals with breast cancer (PMIDs: 33471991 (2021) and 36707629 (2023), see also LOVD (http://databases.lovd.nl/shared/genes/FANCM)) as well as reportedly healthy individuals (PMIDs: 28881617 (2017), 33471991 (2021), and 36707629 (2023), see also LOVD (http://databases.lovd.nl/shared/genes/FANCM)).The frequency of this variant in the general population, 0.0004 (10/24968 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.

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