Submissions for variant NM_032638.5(GATA2):c.299_300delinsTT (p.Gly100Val)

dbSNP: rs1060500084

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000466926	SCV000541499	uncertain significance	Deafness-lymphedema-leukemia syndrome; Monocytopenia with susceptibility to infections	2024-12-03	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 100 of the GATA2 protein (p.Gly100Val). This variant is present in population databases (no rsID available, gnomAD 0.001%). 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: 404071). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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	RCV000500768	SCV000594921	uncertain significance	not specified	2015-11-19	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003392266	SCV004110472	uncertain significance	GATA2-related disorder	2023-01-10	criteria provided, single submitter	clinical testing	The GATA2 c.299_300delinsTT variant is predicted to result in an in-frame deletion and insertion. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
GeneDx	RCV004820030	SCV005440939	uncertain significance	not provided	2024-06-25	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV004984888	SCV005596909	uncertain significance	Inborn genetic diseases	2024-12-08	criteria provided, single submitter	clinical testing	The c.299_300delGGinsTT variant, located in coding exon 2 of the GATA2 gene, results from an in-frame deletion of GG and insertion of TT at nucleotide positions 299 to 300. This results in the substitution of the glycine residue for a valine residue at codon 100, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the available evidence, the clinical significance of this variant remains unclear.
GenomeConnect - Invitae Patient Insights Network	RCV000466926	SCV004228725	not provided	Deafness-lymphedema-leukemia syndrome; Monocytopenia with susceptibility to infections		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 08-07-2020 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.