Submissions for variant NM_032638.5(GATA2):c.1341C>G (p.Ser447Arg)

dbSNP: rs1338194519

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Johns Hopkins Genomics, Johns Hopkins University	RCV003486391	SCV004239088	likely pathogenic	Myelodysplastic syndrome	2023-08-11	criteria provided, single submitter	clinical testing	The GATA2 c.1341C>G variant has not been reported in the literature, to our knowledge. However two other nucleotide changes (c.1341C>A and c.1339A>C) resulting in the same amino acid change p.Ser447Arg have been reported in association with GATA2-related disease. Additionally, in vitro functional testing supports a deleterious role for GATA2 p.Ser447Arg, although additional studies replicating these findings are lacking at this time. GATA2 c.1341C>G is absent from a large population dataset, and has not been reported in ClinVar6. Of two bioinformatics tools queried, one predicts that the substitution would be damaging while the other predicts that it would be tolerated, but these algorithms have low specificity, especially for predicting gain of function or dominant negative variants. The serine residue at this position is evolutionarily conserved across most of the species assessed. This GATA2 variant was found to occur de novo in a patient with GATA2-related disease tested at our lab. We consider c.1341C>G; p.Ser447Arg in GATA2 to be likely pathogenic.