ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.5770A>T (p.Thr1924Ser)

gnomAD frequency: 0.00006  dbSNP: rs747103379
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001222480 SCV001394579 uncertain significance Fanconi anemia 2023-03-03 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 950711). 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 serine 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. This variant has not been reported in the literature in individuals affected with FANCM-related conditions. This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 1924 of the FANCM protein (p.Thr1924Ser). This variant is present in population databases (rs747103379, gnomAD 0.005%).
GeneDx RCV001773500 SCV002001279 uncertain significance not provided 2021-12-02 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with ovarian cancer (Dicks 2017); This variant is associated with the following publications: (PMID: 28881617)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001773500 SCV004218829 uncertain significance not provided 2023-04-12 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.000046 (6/129052 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In a large-scale breast cancer association study, the variant was observed in an individual with breast cancer as well as 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 benign. Based on the available information, we are unable to determine the clinical significance of this variant.

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