Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001305887 | SCV001495235 | uncertain significance | Fanconi anemia | 2022-08-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1440 of the FANCD2 protein (p.Gly1440Ser). This variant is present in population databases (rs376442380, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with FANCD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1008533). 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. 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. |
Fulgent Genetics, |
RCV002504465 | SCV002816446 | uncertain significance | Fanconi anemia complementation group D2 | 2022-04-05 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV003151298 | SCV003839516 | uncertain significance | not specified | 2022-07-14 | no assertion criteria provided | clinical testing | DNA sequence analysis of the FANCD2 gene demonstrated a sequence change, c.4318G>A, in exon 43 that results in an amino acid change, p.Gly1440Ser. This sequence change does not appear to have been previously described in individuals with FANCD2-related disorders. This sequence change has been described in the gnomAD database with a frequency of 0.009% in the European subpopulation (dbSNP rs376442380). The p.Gly1440Ser change affects a poorly conserved amino acid residue located in a domain of the FANCD2 protein that is not known to be functional. The p.Gly1440Ser substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, Align GVGD, REVEL). Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Gly1440Ser change remains unknown at this time. |