ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.1265G>A (p.Arg422His)

dbSNP: rs570510177
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001771460 SCV002002722 uncertain significance not provided 2021-03-24 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
Labcorp Genetics (formerly Invitae), Labcorp RCV002540546 SCV002994784 uncertain significance Fanconi anemia 2022-08-05 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with FANCM-related conditions. 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: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine 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: 1314229). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 422 of the FANCM protein (p.Arg422His).
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001771460 SCV004218716 uncertain significance not provided 2023-08-11 criteria provided, single submitter clinical testing This variant has not been reported in individuals with FANCM-related conditions in the published literature. In a breast cancer case-control study, the variant has only been observed in an unaffected control (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/FANCM)). It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). 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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