NM_032638.5(GATA2):c.1370C>T (p.Thr457Met) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 31, 2024
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:: RCV000691681.7

Allele description [Variation Report for NM_032638.5(GATA2):c.1370C>T (p.Thr457Met)]

NM_032638.5(GATA2):c.1370C>T (p.Thr457Met)

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.1370C>T (p.Thr457Met)

HGVS:

NC_000003.12:g.128481092G>A
NG_029334.1:g.17096C>T
NM_001145661.1:c.1370C>T
NM_001145661.2:c.1370C>T
NM_001145662.1:c.1328C>T
NM_032638.5:c.1370C>TMANE SELECT
NP_001139133.1:p.Thr457Met
NP_001139134.1:p.Thr443Met
NP_116027.2:p.Thr457Met
NP_116027.2:p.Thr457Met
LRG_295t1:c.1370C>T
LRG_295t2:c.1370C>T
LRG_295:g.17096C>T
LRG_295p2:p.Thr457Met
NC_000003.11:g.128199935G>A
NM_032638.4:c.1370C>T
NM_032638.5:c.1370C>T

Protein change:

T443M

Links:

dbSNP: rs139415862

NCBI 1000 Genomes Browser:

rs139415862

Molecular consequence:

NM_001145661.2:c.1370C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001145662.1:c.1328C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_032638.5:c.1370C>T - 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

Recent activity

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Amphimas ferrugineus voucher F.J.Breteler 15369 (WAG) tRNA-Leu (trnL) gene, intr...
Amphimas ferrugineus voucher F.J.Breteler 15369 (WAG) tRNA-Leu (trnL) gene, intron; chloroplast
gi|1035440983|gb|KU324665.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000819470	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 31, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31958074, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000819470

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 31, 2024)

germline

clinical testing

PubMed (2)
[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

Identification of germline and somatic mutations in pancreatic adenosquamous carcinoma using whole exome sequencing.

Ma H, Song B, Guo S, Li G, Jin G.

Cancer Biomark. 2020;27(3):389-397. doi: 10.3233/CBM-190236.

PubMed [citation]

PMID:: 31958074

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000819470.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 457 of the GATA2 protein (p.Thr457Met). This variant is present in population databases (rs139415862, gnomAD 0.007%). This missense change has been observed in individual(s) with pancreatic cancer (PMID: 31958074). ClinVar contains an entry for this variant (Variation ID: 570747). 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 with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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