Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001796439 | SCV001507547 | likely pathogenic | Cyclical neutropenia; Neutropenia, severe congenital, 1, autosomal dominant | 2024-01-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp201Alafs*11) in the ELANE gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 67 amino acid(s) of the ELANE protein. This variant is not present in population databases (gnomAD no frequency). 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: 1017714). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant is located in a region of the ELANE protein where a significant number of ELANE nonsense and -1/+2 frameshift mutations have been reported in association with autosomal dominant ELANE-related neutropenia (PMID: 33513358, 23463630, 34340247). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |