ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.808C>T (p.Arg270Cys)

gnomAD frequency: 0.00003  dbSNP: rs751006401
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000823328 SCV000964182 uncertain significance Fanconi anemia 2024-11-02 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 270 of the FANCM protein (p.Arg270Cys). This variant is present in population databases (rs751006401, gnomAD 0.09%). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 31921681, 32994724). ClinVar contains an entry for this variant (Variation ID: 665116). 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 RCV001593019 SCV001814522 uncertain significance not provided 2024-09-17 criteria provided, single submitter clinical testing Observed in individuals with breast, ovarian, or endometrial cancer (PMID: 28881617, 32994724, 36293153); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32994724, 28881617, 36293153, 31921681, 33471991)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001593019 SCV004218845 uncertain significance not provided 2024-10-25 criteria provided, single submitter clinical testing The FANCM c.808C>T (p.Arg270Cys) variant has been reported in the published literature in individuals with hereditary breast and/or ovarian cancer (PMID: 28881617 (2017), 31921681 (2019), 32994724 (2020), 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared), 36707629 (2023)) and endometrial cancer (PMID: 36293153 (2022)). This variant has also been observed in reportedly healthy individuals (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared)). The frequency of this variant in the general population, 0.0009 (31/34584 chromosomes in Admixed 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.
Fulgent Genetics, Fulgent Genetics RCV005004452 SCV005629801 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2024-02-02 criteria provided, single submitter clinical testing

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