NM_032638.5(GATA2):c.1148dup (p.Asn383fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 9, 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:: RCV002815853.3

Allele description [Variation Report for NM_032638.5(GATA2):c.1148dup (p.Asn383fs)]

NM_032638.5(GATA2):c.1148dup (p.Asn383fs)

Gene:

GATA2:GATA binding protein 2 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

3q21.3

Genomic location:

Preferred name:

NM_032638.5(GATA2):c.1148dup (p.Asn383fs)

HGVS:

NC_000003.12:g.128481315dup
NG_029334.1:g.16874dup
NM_001145661.2:c.1148dup
NM_001145662.1:c.1106dup
NM_032638.5:c.1148dupMANE SELECT
NP_001139133.1:p.Asn383Lysfs
NP_001139133.1:p.Asn383fs
NP_001139134.1:p.Asn369fs
NP_116027.2:p.Asn383Lysfs
NP_116027.2:p.Asn383fs
LRG_295t1:c.1147dup
LRG_295t2:c.1147dup
LRG_295:g.16874dup
LRG_295p1:p.Asn383Lysfs
LRG_295p2:p.Asn383Lysfs
NC_000003.11:g.128200156_128200157insT
NC_000003.11:g.128200158dup
NM_001145661.1:c.1147dup
NM_032638.4:c.1147dup

Protein change:

N369fs

Molecular consequence:

NM_001145661.2:c.1148dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001145662.1:c.1106dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_032638.5:c.1148dup - frameshift variant - [Sequence Ontology: SO:0001589]

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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uncharacterized protein LOC112031151 [Quercus suber]
uncharacterized protein LOC112031151 [Quercus suber]
gi|1344071628|ref|XP_023919605.1|

Protein
calcium-dependent protein kinase SK5-like [Cucurbita maxima]
calcium-dependent protein kinase SK5-like [Cucurbita maxima]
gi|1281057143|ref|XP_022970875.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003210544	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 9, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 22430350, 22533337, 24077845, 25624456, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003210544

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 9, 2022)

germline

clinical testing

PubMed (5)
[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

GATA-2 anomaly and clinical phenotype of a sporadic case of lymphedema, dendritic cell, monocyte, B- and NK-cell (DCML) deficiency, and myelodysplasia.

Ishida H, Imai K, Honma K, Tamura S, Imamura T, Ito M, Nonoyama S.

Eur J Pediatr. 2012 Aug;171(8):1273-6. doi: 10.1007/s00431-012-1715-7. Epub 2012 Mar 21.

PubMed [citation]

PMID:: 22430350

Marked genetic heterogeneity in familial myelodysplasia/acute myeloid leukaemia.

Holme H, Hossain U, Kirwan M, Walne A, Vulliamy T, Dokal I.

Br J Haematol. 2012 Jul;158(2):242-248. doi: 10.1111/j.1365-2141.2012.09136.x. Epub 2012 Apr 26.

PubMed [citation]

PMID:: 22533337

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003210544.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant is not present in population databases (gnomAD no frequency). 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.Arg396Gln) have been determined to be pathogenic (PMID: 22430350, 22533337, 24077845, 25624456). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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 sequence change results in a frameshift in the GATA2 gene (p.Asn383Lysfs*153). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 98 amino acid(s) of the GATA2 protein and extend the protein by 54 additional amino acid residues.

#	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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