ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.3556A>G (p.Arg1186Gly)

gnomAD frequency: 0.00001  dbSNP: rs748713183
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001244123 SCV001417323 likely benign Fanconi anemia 2024-01-04 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002480822 SCV002787320 uncertain significance Fanconi anemia complementation group A 2022-03-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003230651 SCV003928800 uncertain significance not specified 2023-04-29 criteria provided, single submitter clinical testing Variant summary: FANCA c.3556A>G (p.Arg1186Gly) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.9e-05 in 246038 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in FANCA causing Fanconi Anemia (4.9e-05 vs 0.0022), allowing no conclusion about variant significance. c.3556A>G has been reported in the literature as a VUS of germline origin in settings of whole exome sequencing in at-least one individual affected with head and neck carcinomas (HNSCC) (example, Cury_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 publication has been ascertained in the context of this evaluation (PMID: 34598035). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (VUS, n=2; Likely benign, n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.
Natera, Inc. RCV001244123 SCV002092523 uncertain significance Fanconi anemia 2020-01-30 no assertion criteria provided clinical testing

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