Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001314783 | SCV001505331 | uncertain significance | Autosomal recessive severe congenital neutropenia due to CSF3R deficiency | 2023-03-08 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1015863). This variant has not been reported in the literature in individuals affected with CSF3R-related conditions. This variant is present in population databases (rs200059719, gnomAD 0.08%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 21 of the CSF3R protein (p.Gly21Arg). |
St. |
RCV001314783 | SCV005402429 | uncertain significance | Autosomal recessive severe congenital neutropenia due to CSF3R deficiency | 2024-02-24 | criteria provided, single submitter | clinical testing | The CSF3R c.61G>A (p.Gly21Arg) missense change has a maximum subpopulation frequency of 0.080% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with CSF3R-related severe congenital neutropenia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |