Submissions for variant NM_001972.4(ELANE):c.640G>A (p.Gly214Arg)

dbSNP: rs137854451

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000214338	SCV000278970	pathogenic	not provided	2015-06-30	criteria provided, single submitter	clinical testing	The G214R missense mutation in the ELANE gene has been reported previously (as G185R) in association with congenital neutropenia (Dale et al., 2000; Bellanné-Chantelot et al., 2004). The G214R mutation was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.
Beijing Key Laboratry for Genetics of Birth Defects, Beijing Children's Hospital	RCV000018232	SCV001499920	pathogenic	Neutropenia, severe congenital, 1, autosomal dominant	2020-12-20	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001336413	SCV001529791	pathogenic	Cyclical neutropenia	2018-04-27	criteria provided, single submitter	clinical testing	This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant was previously reported as disease-causing [PMID: 11001877, 15657182, 28073911, described as p.G185R]
Labcorp Genetics (formerly Invitae), Labcorp	RCV001851904	SCV002238566	pathogenic	Cyclical neutropenia; Neutropenia, severe congenital, 1, autosomal dominant	2024-07-03	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 214 of the ELANE protein (p.Gly214Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of severe congenital neutropenia (PMID: 11001877, 16079102, 30386760). This variant is also known as G185R. ClinVar contains an entry for this variant (Variation ID: 16748). 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 with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ELANE function (PMID: 15657182, 28073911). This variant disrupts the p.Gly214 amino acid residue in ELANE. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23463630, 25427142). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000018232	SCV003924305	pathogenic	Neutropenia, severe congenital, 1, autosomal dominant	2023-05-08	criteria provided, single submitter	research
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000018232	SCV004801916	pathogenic	Neutropenia, severe congenital, 1, autosomal dominant	2024-03-25	criteria provided, single submitter	clinical testing
OMIM	RCV000018232	SCV000038511	pathogenic	Neutropenia, severe congenital, 1, autosomal dominant	2008-01-01	no assertion criteria provided	literature only