ClinVar Miner

Submissions for variant NM_003467.3(CXCR4):c.956_957del (p.Ser319fs)

dbSNP: rs1684841455
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001035858 SCV001199197 pathogenic Warts, hypogammaglobulinemia, infections, and myelokathexis 2023-10-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser319Cysfs*24) in the CXCR4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 34 amino acid(s) of the CXCR4 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with warts, hypogammaglobulinemia, immunodeficiency, myelokathexis (WHIM) syndrome (PMID: 27484033). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 835055). 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 premature translational stop signal affects CXCR4 function (Zmajkovicova K et al. Dec 2021. American Society of Hematology Session 203. Comprehensive in Vitro Characterization of CXCR4-WHIM variants to Decipher Genotype–Phenotype Correlations in W­H­I­M Syndrome.). 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.

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