Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Pathology Research Laboratory, |
RCV001541961 | SCV001760596 | likely pathogenic | Deafness-lymphedema-leukemia syndrome; GATA2 deficiency with susceptibility to MDS/AML | 2021-07-06 | criteria provided, single submitter | curation | PVS1_Moderate, PS4_Supporting, PM2 |
Genetics and Molecular Pathology, |
RCV002466683 | SCV002761431 | likely pathogenic | Acute myeloid leukemia | 2020-02-27 | criteria provided, single submitter | clinical testing | The GATA2:c.1322_1325dup variant is a four base duplication which introduces a frameshift at position 442 in the protein. The variant has not been described in the literature to date and is absent from population databases (PM2). The variant is not present in ClinVar or HGMD (2019.4). This frameshift variant is in exon 6 of 6 and leads extension of the reading frame by 55 amino acids, introducing a termination codon 94 amino acids downstream from the duplication site. This is predicted to have a detrimental effect on the resulting protein and disrupt the C-terminal domain. In addition, a missense variant, p.Ser447Arg, has been reported downstream of this variant in association with disease (PMID: 26702063). However, in the absence of functional or segregation studies, the effect on the resulting protein and clinical significance is uncertain. The GATA2:c.1322_1325dup variant is classified as a Variant of Uncertain Clinical Significance (VUS) (PM2). |
Gene |
RCV002508316 | SCV002817852 | uncertain significance | not provided | 2022-06-29 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation as the last 39 amino acids are replaced with 94 different amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously published as pathogenic or benign to our knowledge |