Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001927193 | SCV002164377 | pathogenic | Warts, hypogammaglobulinemia, infections, and myelokathexis | 2023-09-15 | criteria provided, single submitter | clinical testing | This sequence change results in a frameshift in the CXCR4 gene (p.Ser339Leufs*27). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 14 amino acid(s) of the CXCR4 protein and extend the protein by 12 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CXCR4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1393639). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this frameshift affects CXCR4 function (external communication). This variant is located in a region of the CXCR4 protein where a significant number of CXCR4 nonsense and frameshift mutations have been reported in association with autosomal dominant WHIM syndrome (PMID: 31313072, 32784523, 35947323, 36089616). For these reasons, this variant has been classified as Pathogenic. |