Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000228027 | SCV000291158 | uncertain significance | Fanconi anemia | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 852 of the FANCD2 protein (p.Pro852Arg). This variant is present in population databases (rs375827113, gnomAD 0.04%). 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: 241736). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FANCD2 protein function with a negative predictive value of 80%. 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. |
Baylor Genetics | RCV001336827 | SCV001530328 | uncertain significance | Fanconi anemia complementation group D2 | 2018-01-29 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Genetic Services Laboratory, |
RCV001820771 | SCV002068118 | uncertain significance | not specified | 2020-04-24 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the FANCD2 gene demonstrated a sequence change, c.2555C>G, in exon 27 that results in an amino acid change, p.Pro852Arg. This sequence change does not appear to have been previously described in patients with FANCD2-related disorders and has been described in the EXAC database with a low population frequency of 0.040% in the African subpopulation (dbSNP rs375827113). The p.Pro852Arg change affects a moderately conserved amino acid residue located in a domain of the FANCD2 protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Pro852Arg substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Pro852Arg change remains unknown at this time. |
Fulgent Genetics, |
RCV001336827 | SCV002814180 | uncertain significance | Fanconi anemia complementation group D2 | 2022-05-26 | criteria provided, single submitter | clinical testing |