ClinVar Miner

Submissions for variant NM_001018115.3(FANCD2):c.2372A>G (p.Asn791Ser)

gnomAD frequency: 0.00003  dbSNP: rs758718558
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago 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, 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, LabCorp 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.

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