ClinVar Miner

Submissions for variant NM_001018115.3(FANCD2):c.4281+107T>C

gnomAD frequency: 0.00004  dbSNP: rs767893462
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001053491 SCV001217757 uncertain significance Fanconi anemia 2022-07-18 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1463 of the FANCD2 protein (p.Leu1463Pro). This variant is present in population databases (rs767893462, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with FANCD2-related conditions. This missense change has been observed to co-occur in individuals with a different variant in FANCD2 that has been determined to be pathogenic (Invitae), but the significance of this finding is unclear. ClinVar contains an entry for this variant (Variation ID: 849509). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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 RCV001819775 SCV002066648 uncertain significance not specified 2020-11-02 criteria provided, single submitter clinical testing DNA sequence analysis of the FANCD2 gene demonstrated a sequence change, c.4388T>C, in exon 43 that results in an amino acid change, p.Leu1463Pro. 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 0.0036% (dbSNP rs767893462). The p.Leu1463Pro change affects a poorly conserved amino acid residue located in a domain of the FANCD2 protein that is not known to be functional. The p.Leu1463Pro 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.Leu1463Pro change remains unknown at this time.
Sema4, Sema4 RCV001053491 SCV002529533 uncertain significance Fanconi anemia 2021-09-13 criteria provided, single submitter curation
Fulgent Genetics, Fulgent Genetics RCV002489629 SCV002789000 uncertain significance Fanconi anemia complementation group D2 2022-04-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV003243442 SCV003951028 uncertain significance Inborn genetic diseases 2023-03-16 criteria provided, single submitter clinical testing The c.4388T>C (p.L1463P) alteration is located in exon 43 (coding exon 42) of the FANCD2 gene. This alteration results from a T to C substitution at nucleotide position 4388, causing the leucine (L) at amino acid position 1463 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.