ClinVar Miner

Submissions for variant NM_001972.4(ELANE):c.104G>A (p.Arg35Gln)

gnomAD frequency: 0.00009  dbSNP: rs375350474
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002009232 SCV002292872 uncertain significance Cyclical neutropenia; Neutropenia, severe congenital, 1, autosomal dominant 2025-01-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 35 of the ELANE protein (p.Arg35Gln). This variant is present in population databases (rs375350474, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ELANE-related conditions. ClinVar contains an entry for this variant (Variation ID: 1506968). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ELANE protein function with a negative predictive value of 95%. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV002009232 SCV003919917 uncertain significance Cyclical neutropenia; Neutropenia, severe congenital, 1, autosomal dominant 2022-10-27 criteria provided, single submitter clinical testing This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF: 0.03% [13/41464]; https://gnomad.broadinstitute.org/variant/19-852912-G-A?dataset=gnomad_r3), and in ClinVar (Variation ID: 1506986). Evolutationary conservation and computational prediction tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Mayo Clinic Laboratories, Mayo Clinic RCV003481249 SCV004224512 uncertain significance not provided 2022-02-22 criteria provided, single submitter clinical testing BP4
Ambry Genetics RCV004046193 SCV004863112 likely benign Inborn genetic diseases 2023-12-19 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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