ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.1835A>G (p.Lys612Arg)

gnomAD frequency: 0.00001  dbSNP: rs777736014
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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 RCV000815164 SCV000955611 uncertain significance Fanconi anemia 2022-07-24 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 612 of the FANCA protein (p.Lys612Arg). This variant is present in population databases (rs777736014, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with FANCA-related conditions. ClinVar contains an entry for this variant (Variation ID: 658355). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FANCA 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002282378 SCV002570503 uncertain significance not specified 2022-07-05 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001271611 SCV002784539 uncertain significance Fanconi anemia complementation group A 2022-05-08 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478516 SCV004221935 uncertain significance not provided 2023-03-30 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.000027 (3/112108 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in healthy individuals from cancer association studies (PMID: 29641532 (2018), 32546565 (2021)). 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.
Natera, Inc. RCV001271611 SCV001452878 uncertain significance Fanconi anemia complementation group A 2020-09-16 no assertion criteria provided clinical testing

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