Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000500317 | SCV000594689 | uncertain significance | not specified | 2016-05-27 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000796186 | SCV000935688 | uncertain significance | Fanconi anemia | 2022-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 791 of the FANCD2 protein (p.Asn791Ser). This variant is present in population databases (rs758718558, gnomAD 0.1%). 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: 435145). 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 expected to disrupt FANCD2 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. |
Fulgent Genetics, |
RCV002506223 | SCV002816174 | uncertain significance | Fanconi anemia complementation group D2 | 2022-01-05 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000500317 | SCV004813316 | uncertain significance | not specified | 2024-02-15 | criteria provided, single submitter | clinical testing | Variant summary: FANCD2 c.2372A>G (p.Asn791Ser) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.1e-05 in 1604192 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in FANCD2 causing Fanconi Anemia (1.1e-05 vs 0.00048), allowing no conclusion about variant significance. c.2372A>G has been reported in the literature in an individual affected with Fanconi Anemia (Chang_2023). This report does not provide unequivocal conclusions about association of the variant with Fanconi Anemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 36463940). ClinVar contains an entry for this variant (Variation ID: 435145). Based on the evidence outlined above, the variant was classified as uncertain significance. |