ClinVar Miner

Submissions for variant NM_032638.5(GATA2):c.1085G>C (p.Arg362Pro)

dbSNP: rs867160952
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Pathology Research Laboratory, SA Pathology RCV001542119 SCV001760787 likely pathogenic Deafness-lymphedema-leukemia syndrome; GATA2 deficiency with susceptibility to MDS/AML 2021-07-06 criteria provided, single submitter curation PS4_Moderate, PM1, PM2, PP3
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV005232397 SCV005877977 likely pathogenic not provided 2024-03-29 criteria provided, single submitter clinical testing The GATA2 c.1085G>C; p.Arg362Pro variant (rs867160952) is reported in the literature in a family with GATA2 deficiency (Donadieu 2018). It has also been reported in three individuals affected with pediatric AML, including once as a confirmed somatic variant (Luesink 2012, Shiba 2014). This variant is also reported in ClinVar (Variation ID: 1184157). This variant is absent from the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. Computational analyses predict that this variant is deleterious (REVEL: 0.978). Based on available information, this variant is considered to be likely pathogenic. References: Donadieu J et al. Natural history of GATA2 deficiency in a survey of 79 French and Belgian patients. Haematologica. 2018 Aug. PMID: 29724903. Luesink M et al. High GATA2 expression is a poor prognostic marker in pediatric acute myeloid leukemia. Blood. 2012 Sep 6. PMID: 22786876. Shiba N et al. Mutations of the GATA2 and CEBPA genes in paediatric acute myeloid leukaemia. Br J Haematol. 2014 Jan. PMID: 24033149.
PreventionGenetics, part of Exact Sciences RCV004728765 SCV005335652 pathogenic GATA2-related disorder 2024-05-18 no assertion criteria provided clinical testing The GATA2 c.1085G>C variant is predicted to result in the amino acid substitution p.Arg362Pro. This variant has been reported in two siblings with Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) (Donadieu et al. 2018. PubMed ID: 29724903. Supplementary data). This variant has also been reported in individuals with pediatric AML (Luesink et al. 2012. PubMed ID: 22786876; https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.12559). Functional study showed that this variant could weaken differentiation-regulatory activity (Katsumura et al. 2024. PubMed ID: 38422019). Different missense substitutions at this same codon (p.Arg362Gln; p.Arg362Gly) have been reported in individuals with GATA2-related conditions (Weinberg et al. 2019. PubMed ID: 31309983; Luesink et al. 2012. PubMed ID: 22786876; https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.12559) suggesting that substitution of amino acid residue p.Arg362 is not tolerated. This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as pathogenic.

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