Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Diagnostics Laboratory, |
RCV000012820 | SCV000891278 | likely pathogenic | Fanconi anemia complementation group D2 | 2016-11-21 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000809924 | SCV000950107 | pathogenic | Fanconi anemia | 2023-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 302 of the FANCD2 protein (p.Arg302Trp). This variant is present in population databases (rs121917787, gnomAD 0.002%). This missense change has been observed in individual(s) with Fanconi anemia (PMID: 11239453, 22720145, 25703294; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 12040). 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 with a positive predictive value of 80%. Experimental studies have shown that this missense change affects FANCD2 function (PMID: 11239453, 17308347, 22828868). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Revvity Omics, |
RCV000012820 | SCV002024586 | likely pathogenic | Fanconi anemia complementation group D2 | 2019-05-02 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000012820 | SCV004196720 | pathogenic | Fanconi anemia complementation group D2 | 2023-10-10 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000012820 | SCV000033060 | pathogenic | Fanconi anemia complementation group D2 | 2001-02-01 | no assertion criteria provided | literature only | |
Leiden Open Variation Database | RCV000012820 | SCV001364772 | pathogenic | Fanconi anemia complementation group D2 | 2020-02-28 | no assertion criteria provided | curation | Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach. |