ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.2851C>T (p.Arg951Trp) (rs755546887)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669024 SCV000793720 likely pathogenic Fanconi anemia, complementation group A 2017-08-29 criteria provided, single submitter clinical testing
Invitae RCV000466964 SCV000547771 pathogenic Fanconi anemia 2018-02-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 951 of the FANCA protein (p.Arg951Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. While this variant is present in population databases (rs755546887), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in several individuals affected with Fanconi anemia (PMID: 22778927, 17924555, 24584348, 26799702). In two of the cases this variant was shown to be on the opposite chromosome (in trans) from a different pathogenic variant (PMID: 17924555, 24584348). One other affected individual was reported to be homozygous for this variant (PMID: 26799702). These findings are consistent with autosomal recessive inheritance, and suggest that this variant contributes to disease. Experimental studies have shown that this missense change can disrupt the normal functioning of the FANCA protein (PMID: 24349332). For these reasons, this variant has been classified as Pathogenic.

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.