ClinVar Miner

Submissions for variant NM_001113378.2(FANCI):c.2687G>C (p.Gly896Ala)

gnomAD frequency: 0.00003  dbSNP: rs751233975
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001244711 SCV001417953 uncertain significance Fanconi anemia 2022-08-05 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 896 of the FANCI protein (p.Gly896Ala). This variant is present in population databases (rs751233975, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with FANCI-related conditions. ClinVar contains an entry for this variant (Variation ID: 969376). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine 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.
Ambry Genetics RCV002564088 SCV003597129 uncertain significance Inborn genetic diseases 2022-01-07 criteria provided, single submitter clinical testing The c.2687G>C (p.G896A) alteration is located in exon 25 (coding exon 24) of the FANCI gene. This alteration results from a G to C substitution at nucleotide position 2687, causing the glycine (G) at amino acid position 896 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Neuberg Centre For Genomic Medicine, NCGM RCV003448384 SCV004176671 uncertain significance Fanconi anemia complementation group I 2023-02-14 criteria provided, single submitter clinical testing The missense c.2687G>C (p.Gly896Ala) variant inFANCI gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Gly896Ala variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid change p.Gly896Ala in FANCI is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Gly at position 896 is changed to a Ala changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS).

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