Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV001822472 | SCV002065151 | uncertain significance | not specified | 2021-03-15 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the FANCI gene demonstrated a sequence change, c.2918A>G, in exon 27 that results in an amino acid change, p.Gln973Arg. This sequence change is absent from known population databases. The p.Gln973Arg change affects a poorly conserved amino acid residue located in a domain of the FANCI protein that is not known to be functional. The p.Gln973Arg substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change does not appear to have been previously described in patients with FANCI-related disorders. Due to the lack of sufficient evidences, the clinical significance of the p.Gln973Arg change remains unknown at this time. |
Labcorp Genetics |
RCV001869757 | SCV002116013 | uncertain significance | Fanconi anemia | 2023-11-13 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 973 of the FANCI protein (p.Gln973Arg). This variant is not present in population databases (gnomAD no frequency). 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: 1337874). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |