ClinVar Miner

Submissions for variant NM_032638.5(GATA2):c.409C>T (p.Pro137Ser)

gnomAD frequency: 0.00001  dbSNP: rs113166293
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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 RCV000814315 SCV000954718 uncertain significance Deafness-lymphedema-leukemia syndrome; Monocytopenia with susceptibility to infections 2024-04-25 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 137 of the GATA2 protein (p.Pro137Ser). This variant is not present in population databases (gnomAD no frequency). 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: 657659). 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) performed at Invitae indicates that this missense variant is not expected to disrupt GATA2 protein function with a negative predictive value of 95%. 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.
Genetic Services Laboratory, University of Chicago RCV001816891 SCV002065807 uncertain significance not specified 2021-12-14 criteria provided, single submitter clinical testing DNA sequence analysis of the GATA2 gene demonstrated a sequence change, c.409C>T, in exon 3 that results in an amino acid change, p.Pro137Ser. This sequence change does not appear to have been previously described in individuals with GATA2-related disorders and has also not been described in population databases such as ExAC and gnomAD (dbSNP rs113166293). The p.Pro137Ser change affects a poorly conserved amino acid residue located in a domain of the GATA2 protein that is known to be functional. The p.Pro137Ser substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Pro137Ser change remains unknown at this time.

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