ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.1477A>G (p.Ile493Val)

gnomAD frequency: 0.00002  dbSNP: rs762828757
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002017965 SCV002300712 uncertain significance Fanconi anemia 2021-09-02 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 493 of the FANCA protein (p.Ile493Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs762828757, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with FANCA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 RCV002486680 SCV002792170 uncertain significance Fanconi anemia complementation group A 2021-07-12 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV002486680 SCV003919929 uncertain significance Fanconi anemia complementation group A 2022-03-18 criteria provided, single submitter clinical testing This variant has not been reported in the literature but is present in 0.01% (4/30616) of South Asian alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/16-89849504-T-C?dataset=gnomad_r2_1). This variant amino acid Valine (Val) is present in several species and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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.