ClinVar Miner

Submissions for variant NM_032638.5(GATA2):c.1381C>T (p.Pro461Ser)

gnomAD frequency: 0.00001  dbSNP: rs1238679450
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002042085 SCV002110653 uncertain significance Deafness-lymphedema-leukemia syndrome; Monocytopenia with susceptibility to infections 2023-08-11 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 461 of the GATA2 protein (p.Pro461Ser). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1350728). Advanced 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 at Invitae 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV004785341 SCV005402148 uncertain significance GATA2 deficiency with susceptibility to MDS/AML 2024-05-27 criteria provided, single submitter clinical testing The GATA2 c.1381C>T p.Pro461Ser variant has a maximum subpopulation frequency of 0.00089% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been identified in individuals with GATA2-associated phenotypes. 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.

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