ClinVar Miner

Submissions for variant NM_001018115.3(FANCD2):c.817A>G (p.Ile273Val)

gnomAD frequency: 0.00003  dbSNP: rs770985541
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000793655 SCV000933019 uncertain significance Fanconi anemia 2022-09-23 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 273 of the FANCD2 protein (p.Ile273Val). This variant is present in population databases (rs770985541, gnomAD 0.02%). 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: 640600). 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. 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.
Genetic Services Laboratory, University of Chicago RCV001816844 SCV002071752 uncertain significance not specified 2021-07-30 criteria provided, single submitter clinical testing This sequence change does not appear to have been previously described in patients with FANCD2-related disorders and has been described in the gnomAD database with a low population frequency of 0.0077% in the non-Finnish European subpopulation (dbSNP rs770985541). The p.Ile273Val change affects a poorly conserved amino acid residue located in a domain of the FANCD2 protein that is known to be functional. The p.Ile273Val substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Ile273Val change remains unknown at this time.
Fulgent Genetics, Fulgent Genetics RCV002493445 SCV002776662 uncertain significance Fanconi anemia complementation group D2 2021-12-23 criteria provided, single submitter clinical testing

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