NM_032638.5(GATA2):c.550G>C (p.Asp184His) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 25, 2022
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:: RCV003794696.1

Allele description

NM_032638.5(GATA2):c.550G>C (p.Asp184His)

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.550G>C (p.Asp184His)

HGVS:

NC_000003.12:g.128486048C>G
NG_029334.1:g.12140G>C
NM_001145661.2:c.550G>C
NM_001145662.1:c.550G>C
NM_032638.5:c.550G>CMANE SELECT
NP_001139133.1:p.Asp184His
NP_001139133.1:p.Asp184His
NP_001139134.1:p.Asp184His
NP_116027.2:p.Asp184His
NP_116027.2:p.Asp184His
LRG_295t1:c.550G>C
LRG_295t2:c.550G>C
LRG_295:g.12140G>C
LRG_295p1:p.Asp184His
LRG_295p2:p.Asp184His
NC_000003.11:g.128204891C>G
NM_001145661.1:c.550G>C
NM_032638.4:c.550G>C

Protein change:

D184H

Molecular consequence:

NM_001145661.2:c.550G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001145662.1:c.550G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_032638.5:c.550G>C - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004587376	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 25, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004587376

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 25, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV004587376.1

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

Description

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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GATA2 protein function. This variant has not been reported in the literature in individuals affected with GATA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 184 of the GATA2 protein (p.Asp184His).

#	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: Sep 1, 2024

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