ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.2473A>C (p.Ser825Arg)

gnomAD frequency: 0.00013  dbSNP: rs547223696
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000808664 SCV000948778 uncertain significance Fanconi anemia 2023-07-31 criteria provided, single submitter clinical testing 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine 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: 652987). This variant has not been reported in the literature in individuals affected with FANCM-related conditions. This variant is present in population databases (rs547223696, gnomAD 0.1%). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 825 of the FANCM protein (p.Ser825Arg).
Fulgent Genetics, Fulgent Genetics RCV002478877 SCV002787772 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2024-06-19 criteria provided, single submitter clinical testing
GeneDx RCV003148869 SCV003837514 uncertain significance not provided 2024-01-16 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
Ambry Genetics RCV004028650 SCV004869905 uncertain significance Inborn genetic diseases 2023-12-13 criteria provided, single submitter clinical testing The c.2473A>C (p.S825R) alteration is located in exon 14 (coding exon 14) of the FANCM gene. This alteration results from a A to C substitution at nucleotide position 2473, causing the serine (S) at amino acid position 825 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003148869 SCV005626269 uncertain significance not provided 2024-06-10 criteria provided, single submitter clinical testing The FANCM c.2473A>C (p.Ser825Arg) variant has not been reported in individuals with FANCM-related conditions in the published literature. The frequency of this variant in the general population, 0.00097 (33/34024 chromosomes in Latino/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 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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