ClinVar Miner

Submissions for variant NM_021922.3(FANCE):c.598C>T (p.Arg200Cys)

gnomAD frequency: 0.00007  dbSNP: rs763151358
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Predisposition to Colorectal Cancer Group, Institut d’Investigacions Biomediques August Pi i Sunyer RCV000416904 SCV000262604 likely pathogenic Carcinoma of colon 2015-11-01 criteria provided, single submitter clinical testing Variant detected by whole exome sequencing in a family presenting aggregation mainly for colorectal cancer but also for breast cancer
Labcorp Genetics (formerly Invitae), Labcorp RCV000649006 SCV000770827 uncertain significance Fanconi anemia complementation group E 2022-07-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 200 of the FANCE protein (p.Arg200Cys). This variant is present in population databases (rs763151358, gnomAD 0.04%). This missense change has been observed in individual(s) with colorectal cancer and breast cancer (PMID: 27165003). ClinVar contains an entry for this variant (Variation ID: 221623). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV003488462 SCV004241402 uncertain significance not specified 2023-12-13 criteria provided, single submitter clinical testing Variant summary: FANCE c.598C>T (p.Arg200Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 250994 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in FANCE causing Fanconi Anemia (6e-05 vs 0.00048), allowing no conclusion about variant significance. c.598C>T has been reported in the literature in individuals affected with Colon cancer, Breast cancer and other unspecified childhood cancer, without strong evidence for causality (example, Esteban-Jurado_2016, Sylvester_2021). These report(s) do not provide unequivocal conclusions about association of the variant with Fanconi Anemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 27165003, 34687117). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as likely pathogenic, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV000649006 SCV005669096 uncertain significance Fanconi anemia complementation group E 2024-02-28 criteria provided, single submitter clinical testing

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