Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001794455 | SCV000821040 | pathogenic | Cyclical neutropenia; Neutropenia, severe congenital, 1, autosomal dominant | 2023-05-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ELANE protein function. ClinVar contains an entry for this variant (Variation ID: 16740). This variant is also known as p.Ala32Val. This missense change has been observed in individual(s) with congenital neutropenia and/or cyclic neutropenia (PMID: 10581030, 11675333, 19036076, 23463630, 25703294). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 61 of the ELANE protein (p.Ala61Val). |
| Genome Diagnostics Laboratory, |
RCV002262567 | SCV002543408 | pathogenic | Autoinflammatory syndrome | 2018-12-01 | criteria provided, single submitter | clinical testing | |
| Institute of Medical Genetics and Genomics, |
RCV003343600 | SCV004046872 | likely pathogenic | Neutropenia, severe congenital, 1, autosomal dominant | 2023-10-23 | criteria provided, single submitter | clinical testing | This heterozygous mis-sense variant is identified in a 2.6 years girl with recurrent mucosal infection, oral candidiasis, cervical adenopathy, and severe neutropenia with ANC 230, suggestive of congenital neutropenia. This nucleotide change is absent in gnomAD database [PM2]. Insilico prediction [REVEL: 0.5] predicts uncertain nature of this variant. A clinvar entry for this variant is available. This variant is submitted to clinvar database [Variation ID: 16740] with “Pathogenic” interpretation by multiple submitter [PP5]. 9 pathogenic or likely pathogenic reported variants are found surrounding this region in exon 2 without any mis-sense benign change, considering this as a hotspot region [PM1]. PMID [23463630] Based on the clinical correlation and available evidence, this variant is classified as "Likely Pathogenic" |
| OMIM | RCV000018224 | SCV000038503 | pathogenic | Cyclical neutropenia | 1999-12-01 | no assertion criteria provided | literature only |