Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001244711 | SCV001417953 | uncertain significance | Fanconi anemia | 2022-08-05 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 969376). This variant has not been reported in the literature in individuals affected with FANCI-related conditions. This variant is present in population databases (rs751233975, gnomAD 0.02%). 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). |
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 Supratech Reference Laboratories Pvt Ltd, |
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). |