Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000706855 | SCV000835929 | pathogenic | Lymphedema, primary, with myelodysplasia; Dendritic cell, monocyte, B lymphocyte, and natural killer lymphocyte deficiency | 2018-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with methionine at codon 354 of the GATA2 protein (p.Thr354Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with myelodysplastic syndrome and acute myeloid leukemia in several large families (PMID: 21892162, 21670465). Additionally, this variant has been reported in a patient with GATA2 deficiency (PMID: 23365458). ClinVar contains an entry for this variant (Variation ID: 29711). Experimental studies have shown that this missense change reduces GATA2 transactivation ability and inhibits apoptosis while enabling cell proliferation and survival (PMID: 21892162, 25676417). For these reasons, this variant has been classified as Pathogenic. |
Prevention |
RCV000984820 | SCV001132702 | pathogenic | not provided | 2015-07-23 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000022561 | SCV000043850 | pathogenic | Dendritic cell, monocyte, B lymphocyte, and natural killer lymphocyte deficiency | 2011-09-08 | no assertion criteria provided | literature only | |
OMIM | RCV000022562 | SCV000043851 | risk factor | Myelodysplastic syndrome | 2011-09-08 | no assertion criteria provided | literature only | |
OMIM | RCV000022563 | SCV000043852 | risk factor | Leukemia, acute myeloid, susceptibility to | 2011-09-08 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000426616 | SCV000504647 | likely pathogenic | Acute myeloid leukemia | 2014-10-02 | no assertion criteria provided | literature only |