NM_032638.5(GATA2):c.1018-1G>T AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 19, 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:: RCV003764625.2

Allele description [Variation Report for NM_032638.5(GATA2):c.1018-1G>T]

NM_032638.5(GATA2):c.1018-1G>T

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.1018-1G>T

HGVS:

NC_000003.12:g.128481945C>A
NG_029334.1:g.16243G>T
NM_001145661.2:c.1018-1G>T
NM_001145662.1:c.1018-43G>T
NM_032638.5:c.1018-1G>TMANE SELECT
LRG_295t1:c.1018-1G>T
LRG_295:g.16243G>T
NC_000003.11:g.128200788C>A
NM_001145661.1:c.1018-1G>T

Nucleotide change:

IVS4AS, G-T, -1

Links:

OMIM: 137295.0008; dbSNP: rs869320668

NCBI 1000 Genomes Browser:

rs869320668

Molecular consequence:

NM_001145662.1:c.1018-43G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001145661.2:c.1018-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_032638.5:c.1018-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]

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

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uroc1 urocanate hydratase 1 [Danio rerio]
uroc1 urocanate hydratase 1 [Danio rerio]
Gene ID:556744

Gene
collectin-12 isoform X1 [Homo sapiens]
collectin-12 isoform X1 [Homo sapiens]
gi|767997888|ref|XP_011524043.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004569784	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 19, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16199547, 23223431, 21670465, 21765025, 26022708, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004569784

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 19, 2023)

germline

clinical testing

PubMed (6)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

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 (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004569784.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change affects an acceptor splice site in intron 4 of the GATA2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and 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). Disruption of this splice site has been observed in individuals with GATA2-related conditions (PMID: 21670465, 21765025, 26022708). ClinVar contains an entry for this variant (Variation ID: 29716). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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: Sep 29, 2024

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Relating variation to medicine