ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.2651C>G (p.Ser884Cys)

gnomAD frequency: 0.00001  dbSNP: rs776492214
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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 RCV001053998 SCV001218289 uncertain significance Fanconi anemia 2022-06-15 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 884 of the FANCA protein (p.Ser884Cys). This variant is present in population databases (rs776492214, gnomAD 0.006%). 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: 849937). 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 not expected to disrupt FANCA protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Ambry Genetics RCV002553766 SCV003575807 uncertain significance Inborn genetic diseases 2021-11-15 criteria provided, single submitter clinical testing The c.2651C>G (p.S884C) alteration is located in exon 28 (coding exon 28) of the FANCA gene. This alteration results from a C to G substitution at nucleotide position 2651, causing the serine (S) at amino acid position 884 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478680 SCV004221975 uncertain significance not provided 2023-05-10 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.000012 (3/251472 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an unaffected individual (PMID: 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 predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Natera, Inc. RCV001053998 SCV002092592 uncertain significance Fanconi anemia 2020-07-02 no assertion criteria provided clinical testing

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