Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000230807 | SCV000291136 | uncertain significance | Deafness-lymphedema-leukemia syndrome; Monocytopenia with susceptibility to infections | 2024-10-07 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 48 of the GATA2 protein (p.Phe48Ile). This variant is present in population databases (no rsID available, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with GATA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 241720). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GATA2 protein function. 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. |
| ARUP Laboratories, |
RCV001812654 | SCV001471788 | uncertain significance | not provided | 2020-02-27 | criteria provided, single submitter | clinical testing | The GATA2 c.142T>A; p.Phe48Ile variant (rs878855170), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 241720). This variant is found on only six chromosomes (6/244980 alleles) in the Genome Aggregation Database. The phenylalanine at codon 48 is highly conserved, but computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. However, due to limited information, the clinical significance of the p.Phe48Ile variant is uncertain at this time. |
| Gene |
RCV001812654 | SCV003842787 | uncertain significance | not provided | 2022-09-16 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Mayo Clinic Laboratories, |
RCV001812654 | SCV005410392 | uncertain significance | not provided | 2024-01-04 | criteria provided, single submitter | clinical testing | PP3, PM1, PM2_moderate |
| Ambry Genetics | RCV004975357 | SCV005596809 | likely benign | Inborn genetic diseases | 2024-08-20 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |