ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.3250C>T (p.Arg1084Cys)

gnomAD frequency: 0.00001  dbSNP: rs764206631
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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 RCV001346814 SCV001541045 uncertain significance Fanconi anemia 2021-08-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 1084 of the FANCA protein (p.Arg1084Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs764206631, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with FANCA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The cysteine 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478791 SCV004218553 uncertain significance not provided 2023-07-11 criteria provided, single submitter clinical testing In the published literature, this variant has been reported in individuals with ovarian cancer (PMID: 32546565 (2021)). The variant has also been reported as a somatic variant in pancreatic cancer (PMID: 30836094 (2019), melanoma (PMID: 30050716 (2018)), colorectal cancer (PMID: 32799124 (2020)), and breast cancer (PMID: 32903519 (2020)). The frequency of this variant in the general population, 0.000065 (5/ 113288 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. 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.
Fulgent Genetics, Fulgent Genetics RCV005014463 SCV005644725 uncertain significance Fanconi anemia complementation group A 2024-06-20 criteria provided, single submitter clinical testing
Natera, Inc. RCV001346814 SCV002092544 uncertain significance Fanconi anemia 2020-01-13 no assertion criteria provided clinical testing

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