NM_032638.5(GATA2):c.1121G>A (p.Gly374Asp) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 30, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000696775.4

Allele description [Variation Report for NM_032638.5(GATA2):c.1121G>A (p.Gly374Asp)]

NM_032638.5(GATA2):c.1121G>A (p.Gly374Asp)

Gene:

GATA2:GATA binding protein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q21.3

Genomic location:

Preferred name:

NM_032638.5(GATA2):c.1121G>A (p.Gly374Asp)

HGVS:

NC_000003.12:g.128481841C>T
NG_029334.1:g.16347G>A
NM_001145661.2:c.1121G>A
NM_001145662.1:c.1079G>A
NM_032638.5:c.1121G>AMANE SELECT
NP_001139133.1:p.Gly374Asp
NP_001139134.1:p.Gly360Asp
NP_116027.2:p.Gly374Asp
NP_116027.2:p.Gly374Asp
LRG_295t1:c.1121G>A
LRG_295t2:c.1121G>A
LRG_295:g.16347G>A
LRG_295p2:p.Gly374Asp
NC_000003.11:g.128200684C>T
NM_001145661.1:c.1121G>A
NM_032638.4:c.1121G>A
p.Gly374Asp

Protein change:

G360D

Links:

dbSNP: rs1559985057

NCBI 1000 Genomes Browser:

rs1559985057

Molecular consequence:

NM_001145661.2:c.1121G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001145662.1:c.1079G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_032638.5:c.1121G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Deafness-lymphedema-leukemia syndrome
Synonyms:: Lymphedema, primary, with myelodysplasia; Emberger syndrome
Identifiers:: MONDO: MONDO:0013540; MedGen: C3279664; Orphanet: 3226; OMIM: 614038

Name:: Monocytopenia with susceptibility to infections
Synonyms:: MONOCYTOPENIA AND MYCOBACTERIAL INFECTION SYNDROME; MONOCYTOPENIA WITH SUSCEPTIBILITY TO MYCOBACTERIAL, FUNGAL, AND PAPILLOMAVIRUS INFECTIONS AND MYELODYSPLASIA; COMBINED IMMUNODEFICIENCY WITH SUSCEPTIBILITY TO MYCOBACTERIAL, VIRAL, AND FUNGAL INFECTIONS; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0013607; MedGen: C3280030; Orphanet: 228423; OMIM: 614172

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Ovarian Follicle
Ovarian Follicle
An OOCYTE-containing structure in the cortex of the OVARY. The oocyte is enclosed by a layer of GRANULOSA CELLS providing a nourishing microenvironment (FOLLICULAR FLUID). The...<br/>Year introduced: 1999

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000825352	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 30, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32497548, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000825352

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 30, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Familial Emberger Syndrome With Autoimmunity, Hyper-Immunoglobulin E and Lymphatic Impairment Caused by a Novel GATA2 Mutation.

AlGassim M, Al Seraihi AF, AlShaibani A, Conca W, AlShehri S, Abouzied MM, Hamadah I, AlReshoodi S, Dasouki M, Sheikh F.

Hematol Oncol Stem Cell Ther. 2022 Jun 1;15(2):63-65. doi: 10.1016/j.hemonc.2020.05.004. No abstract available.

PubMed [citation]

PMID:: 32497548

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000825352.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is not present in population databases (gnomAD no frequency). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GATA2 protein function. ClinVar contains an entry for this variant (Variation ID: 574759). This missense change has been observed in individual(s) with clinical features of GATA2-related conditions (PMID: 32497548; Invitae). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 374 of the GATA2 protein (p.Gly374Asp).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 28, 2024

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