ClinVar Miner

Submissions for variant NM_021023.6(CFHR3):c.839_840del (p.Ile280fs)

dbSNP: rs781400776
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mayo Clinic Laboratories, Mayo Clinic RCV001509102 SCV001715633 uncertain significance not provided 2022-11-09 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002282556 SCV002570925 uncertain significance not specified 2024-02-16 criteria provided, single submitter clinical testing Variant summary: CFHR3 c.839_840delTA (p.Ile280LysfsX7) results in a premature termination codon in the last exon of the CFHR3 gene, predicted to cause a truncation of the encoded protein. However, the molecular mechanism of disease attributed to CFHR3 is gain-of-function. The variant allele was found at a frequency of 0.0016 in 1519668 control chromosomes in the gnomAD database, including 368 homozygotes. The observed variant frequency is approximately 10-fold of the estimated maximal expected allele frequency for a pathogenic variant in CFHR3 causing Genetic Atypical Hemolytic Uremic Syndrome phenotype (0.00016), strongly suggesting that the variant is benign. c.839_840delTA has been reported in the literature in individuals affected with Genetic Atypical Hemolytic Uremic Syndrome or transplant-associated thrombotic microangiopathy (e.g. Abarrategui-Garrido_2009, Jodele_2020, Haydock_2022). These reports do not provide unequivocal conclusions about association of the variant with Genetic Atypical Hemolytic Uremic Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 1163768). Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV002488312 SCV002775757 uncertain significance Hemolytic uremic syndrome, atypical, susceptibility to, 1; Age related macular degeneration 1 2024-04-15 criteria provided, single submitter clinical testing

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