ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.1742G>A (p.Arg581His)

gnomAD frequency: 0.00007  dbSNP: rs748083548
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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 RCV001036733 SCV001200111 uncertain significance Fanconi anemia 2022-09-08 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 581 of the FANCM protein (p.Arg581His). This variant is present in population databases (rs748083548, gnomAD 0.007%). 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: 835770). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV001772213 SCV002002390 uncertain significance not provided 2024-08-29 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; Observed in an individual with ovarian cancer (PMID: 28881617); This variant is associated with the following publications: (PMID: 28881617)
Fulgent Genetics, Fulgent Genetics RCV002497357 SCV002782355 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2021-09-20 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001772213 SCV004218725 uncertain significance not provided 2022-09-06 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.000025 (7/282598 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual with ovarian cancer (PMID: 28881617 (2017)). In a large-scale breast cancer association study, the variant was observed in an unaffected individual (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/FANCM)). 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 damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

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