NM_032638.5(GATA2):c.1113C>A (p.Asn371Lys) AND multiple conditions

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

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jun 3, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000197751.3

Allele description

NM_032638.5(GATA2):c.1113C>A (p.Asn371Lys)

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.1113C>A (p.Asn371Lys)

HGVS:

NC_000003.12:g.128481849G>T
NG_029334.1:g.16339C>A
NM_001145661.2:c.1113C>A
NM_001145662.1:c.1071C>A
NM_032638.5:c.1113C>AMANE SELECT
NP_001139133.1:p.Asn371Lys
NP_001139134.1:p.Asn357Lys
NP_116027.2:p.Asn371Lys
NP_116027.2:p.Asn371Lys
LRG_295t2:c.1113C>A
LRG_295:g.16339C>A
LRG_295p2:p.Asn371Lys
NC_000003.11:g.128200692G>T
NM_032638.4:c.1113C>A

Protein change:

N357K

Links:

dbSNP: rs376003468

NCBI 1000 Genomes Browser:

rs376003468

Molecular consequence:

NM_001145661.2:c.1113C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001145662.1:c.1071C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_032638.5:c.1113C>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000255374	UCLA Clinical Genomics Center, UCLA - CES	criteria provided, single submitter (Lee et al. (JAMA. 2014))	Likely pathogenic (Jul 16, 2013)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003525660	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 3, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21670465, 24077845, 26702063, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000255374

UCLA Clinical Genomics Center, UCLA - CES

criteria provided, single submitter

(Lee et al. (JAMA. 2014))

Likely pathogenic
(Jul 16, 2013)

unknown

clinical testing

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

SCV003525660

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 3, 2023)

germline

clinical testing

PubMed (4)
[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
Caucasian	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical exome sequencing for genetic identification of rare Mendelian disorders.

Lee H, Deignan JL, Dorrani N, Strom SP, Kantarci S, Quintero-Rivera F, Das K, Toy T, Harry B, Yourshaw M, Fox M, Fogel BL, Martinez-Agosto JA, Wong DA, Chang VY, Shieh PB, Palmer CG, Dipple KM, Grody WW, Vilain E, Nelson SF.

JAMA. 2014 Nov 12;312(18):1880-7. doi: 10.1001/jama.2014.14604.

PubMed [citation]

PMID:: 25326637
PMCID:: PMC4278636

Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome.

Hsu AP, Sampaio EP, Khan J, Calvo KR, Lemieux JE, Patel SY, Frucht DM, Vinh DC, Auth RD, Freeman AF, Olivier KN, Uzel G, Zerbe CS, Spalding C, Pittaluga S, Raffeld M, Kuhns DB, Ding L, Paulson ML, Marciano BE, Gea-Banacloche JC, Orange JS, et al.

Blood. 2011 Sep 8;118(10):2653-5. doi: 10.1182/blood-2011-05-356352. Epub 2011 Jun 13.

PubMed [citation]

PMID:: 21670465
PMCID:: PMC3172785

See all PubMed Citations (5)

Details of each submission

From UCLA Clinical Genomics Center, UCLA - CES, SCV000255374.2

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

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

From Invitae, SCV003525660.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. 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: 216931). This missense change has been observed in individual(s) with GATA2-related conditions and/or myelodysplastic syndrome (PMID: 21670465, 24077845, 26702063; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 371 of the GATA2 protein (p.Asn371Lys).

#	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: Mar 5, 2024

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