ClinVar Miner

Submissions for variant NM_015175.3(NBEAL2):c.6657C>A (p.Phe2219Leu)

gnomAD frequency: 0.00001  dbSNP: rs749279630
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
NIHR Bioresource Rare Diseases, University of Cambridge RCV000852187 SCV000899860 likely pathogenic Gray platelet syndrome 2020-03-01 criteria provided, single submitter research ACMG criteria: PM2, PM3, PP3, PP4
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003330944 SCV004039086 uncertain significance not specified 2023-08-11 criteria provided, single submitter clinical testing Variant summary: NBEAL2 c.6657C>A (p.Phe2219Leu) results in a non-conservative amino acid change to a highly conserved residue (HGMD) located in the BEACH domain (IPR000409) of the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 246950 control chromosomes (gnomAD). c.6657C>A has been reported in the literature in an individual affected with Gray Platelet Syndrome who was reported as compound heterozygous with another variant that has been classified as pathogenic (Downes_2019, Sims_2020). These data suggest the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 32693407, 31064749). One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly 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.