ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.1549C>T (p.Arg517Trp)

gnomAD frequency: 0.00011  dbSNP: rs587778309
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665475 SCV000789605 uncertain significance Fanconi anemia complementation group A 2017-02-07 criteria provided, single submitter clinical testing
Invitae RCV000802124 SCV000941940 uncertain significance Fanconi anemia 2023-11-14 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 517 of the FANCA protein (p.Arg517Trp). This variant is present in population databases (rs587778309, gnomAD 0.05%). This missense change has been observed in individual(s) with Fanconi anemia (PMID: 16611311). ClinVar contains an entry for this variant (Variation ID: 134243). 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 with a positive predictive value of 80%. 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.
Centogene AG - the Rare Disease Company RCV000665475 SCV002059361 uncertain significance Fanconi anemia complementation group A 2016-03-04 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003477503 SCV004221924 uncertain significance not provided 2023-01-03 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.00054 (19/35424 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported to co-occur with a nonsense FANCA variant, in an individual with Fanconi anaemia (PMID: 16611311 (2006)). Additionally, the variant has been reported in a young unaffected individual (PMID: 24728327 (2014)). 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.
ITMI RCV000120916 SCV000085084 not provided not specified 2013-09-19 no assertion provided reference population
Natera, Inc. RCV000665475 SCV001457948 uncertain significance Fanconi anemia complementation group A 2020-09-16 no assertion criteria provided clinical testing

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