ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.3551G>C (p.Arg1184Pro) (rs147672303)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000287104 SCV000399823 uncertain significance Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000484383 SCV000573678 uncertain significance not provided 2018-08-07 criteria provided, single submitter clinical testing The R1184P variant in the FANCA gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R1184P variant is observed in 20/58508 alleles (0.034%) alleles from individuals of European (Non-Finnish) background, in the ExAC dataset (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R1184P variant is a non-conservative amino acid substitution, which occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R1184P as a variant of uncertain significance.
Invitae RCV000287104 SCV000626189 uncertain significance Fanconi anemia 2017-05-04 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 1184 of the FANCA protein (p.Arg1184Pro). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is present in population databases (rs147672303, ExAC 0.03%) but has not been reported in the literature in individuals with a FANCA-related disease. ClinVar contains an entry for this variant (Variation ID: 321335). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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