ClinVar Miner

Submissions for variant NM_001018115.3(FANCD2):c.904C>T (p.Arg302Trp)

gnomAD frequency: 0.00001  dbSNP: rs121917787
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota 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, Revvity 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.

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