ClinVar Miner

Submissions for variant NM_001972.4(ELANE):c.419C>T (p.Ala140Val)

gnomAD frequency: 0.00001  dbSNP: rs538255080
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
Labcorp Genetics (formerly Invitae), Labcorp RCV001796181 SCV000814045 uncertain significance Cyclical neutropenia; Neutropenia, severe congenital, 1, autosomal dominant 2022-05-12 criteria provided, single submitter clinical testing 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. 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 566655). This variant has not been reported in the literature in individuals affected with ELANE-related conditions. This variant is present in population databases (rs538255080, gnomAD 0.006%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 140 of the ELANE protein (p.Ala140Val).
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV004788116 SCV005402093 uncertain significance Neutropenia, severe congenital, 1, autosomal dominant 2024-05-27 criteria provided, single submitter clinical testing The ELANE c.419C>T (p.Ala140Val) missense change has a maximum subpopulation frequency of 0.0055% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with ELANE-related congenital neutropenia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.

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.