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NM_032638.5(GATA2):c.1126_1143+54del AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 13, 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:
RCV003049305.3

Allele description [Variation Report for NM_032638.5(GATA2):c.1126_1143+54del]

NM_032638.5(GATA2):c.1126_1143+54del

Gene:
GATA2:GATA binding protein 2 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
3q21.3
Genomic location:
Preferred name:
NM_032638.5(GATA2):c.1126_1143+54del
HGVS:
  • NC_000003.12:g.128481765_128481836del
  • NG_029334.1:g.16352_16423del
  • NM_001145661.2:c.1126_1143+54del
  • NM_001145662.1:c.1084_1101+54del
  • NM_032638.5:c.1126_1143+54delMANE SELECT
  • LRG_295:g.16352_16423del
  • NC_000003.11:g.128200608_128200679del
Molecular consequence:
  • NM_001145661.2:c.1126_1143+54del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001145662.1:c.1084_1101+54del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_032638.5:c.1126_1143+54del - splice donor variant - [Sequence Ontology: SO:0001575]

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

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003344730Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 13, 2022) 		germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Mutational landscape in children with myelodysplastic syndromes is distinct from adults: specific somatic drivers and novel germline variants.

Pastor V, Hirabayashi S, Karow A, Wehrle J, Kozyra EJ, Nienhold R, Ruzaike G, Lebrecht D, Yoshimi A, Niewisch M, Ripperger T, Göhring G, Baumann I, Schwarz S, Strahm B, Flotho C, Skoda RC, Niemeyer CM, Wlodarski MW.

Leukemia. 2017 Mar;31(3):759-762. doi: 10.1038/leu.2016.342. Epub 2016 Nov 23. No abstract available.

PubMed [citation]
PMID:
27876779
See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003344730.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GATA2 protein in which other variant(s) (p.Arg396Trp) have been determined to be pathogenic (PMID: 21670465, 27876779, 27924436, 29724903, 31732620). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 variant results in the deletion of part of exon 5 (c.1126_1143+54del) of the GATA2 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024