Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002018479 | SCV002303160 | pathogenic | Warts, hypogammaglobulinemia, infections, and myelokathexis | 2022-08-30 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies have shown that this frameshift affects CXCR4 function (external communication). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 1513755). This frameshift has been observed in individual(s) with clinical features consistent with WHIM syndrome (Invitae). 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 results in a frameshift in the CXCR4 gene (p.Ser346Profs*12). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 7 amino acid(s) of the CXCR4 protein and extend the protein by 4 additional amino acid residues. |