NM_032638.5(GATA2):c.1084C>T (p.Arg362Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 29, 2023
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:: RCV001857100.4

Allele description [Variation Report for NM_032638.5(GATA2):c.1084C>T (p.Arg362Ter)]

NM_032638.5(GATA2):c.1084C>T (p.Arg362Ter)

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.1084C>T (p.Arg362Ter)

Other names:

p.Arg362*

HGVS:

NC_000003.12:g.128481878G>A
NG_029334.1:g.16310C>T
NM_001145661.2:c.1084C>T
NM_001145662.1:c.1042C>T
NM_032638.5:c.1084C>TMANE SELECT
NP_001139133.1:p.Arg362Ter
NP_001139134.1:p.Arg348Ter
NP_116027.2:p.Arg362Ter
NP_116027.2:p.Arg362Ter
LRG_295t1:c.1084C>T
LRG_295t2:c.1084C>T
LRG_295:g.16310C>T
LRG_295p2:p.Arg362Ter
NC_000003.11:g.128200721G>A
NM_001145661.1:c.1084C>T
NM_032638.4:c.1084C>T

Protein change:

R348*

Links:

dbSNP: rs1553770510

NCBI 1000 Genomes Browser:

rs1553770510

Molecular consequence:

NM_001145661.2:c.1084C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001145662.1:c.1042C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_032638.5:c.1084C>T - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002247448	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 29, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 21670465, 23223431, 27266944, 29146883, 29724903, 32098966, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002247448

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 29, 2023)

germline

clinical testing

PubMed (7)
[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

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

High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia.

Pasquet M, Bellanné-Chantelot C, Tavitian S, Prade N, Beaupain B, Larochelle O, Petit A, Rohrlich P, Ferrand C, Van Den Neste E, Poirel HA, Lamy T, Ouachée-Chardin M, Mansat-De Mas V, Corre J, Récher C, Plat G, Bachelerie F, Donadieu J, Delabesse E.

Blood. 2013 Jan 31;121(5):822-9. doi: 10.1182/blood-2012-08-447367. Epub 2012 Dec 6.

PubMed [citation]

PMID:: 23223431
PMCID:: PMC3714670

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV002247448.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change creates a premature translational stop signal (p.Arg362*) in the GATA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GATA2 are known to be pathogenic (PMID: 21670465, 23223431). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of GATA2-related conditions (PMID: 27266944, 29146883, 29724903, 32098966). ClinVar contains an entry for this variant (Variation ID: 435281). For these reasons, this variant has been classified as Pathogenic.

#	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 16, 2024

ClinVar

Relating variation to medicine