rs3803

Variant names:

• chr3-128480537-G-A
• rs3803
• NM_032638.5:c.*482C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032638.5(GATA2):​c.*482C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 251,374 control chromosomes in the GnomAD database, including 3,943 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2468 hom., cov: 33)
  • Exomes 𝑓: 0.16 (1475 hom.)
• Consequence: GATA2 NM_032638.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.819
• Publications: 23 publications found

Genes affected

GATA2 (HGNC:4171): (GATA binding protein 2) This gene encodes a member of the GATA family of zinc-finger transcription factors that are named for the consensus nucleotide sequence they bind in the promoter regions of target genes. The encoded protein plays an essential role in regulating transcription of genes involved in the development and proliferation of hematopoietic and endocrine cell lineages. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

GATA2 Gene-Disease associations (from GenCC):

• deafness-lymphedema-leukemia syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• GATA2 deficiency with susceptibility to MDS/AML

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• monocytopenia with susceptibility to infections

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
• acute myeloid leukemia

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• myelodysplastic syndrome

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-128480537-G-A is Benign according to our data. Variant chr3-128480537-G-A is described in ClinVar as Benign. ClinVar VariationId is 343123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA2	NM_032638.5	c.*482C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000341105.7	NP_116027.2
GATA2	NM_001145661.2	c.*482C>T		3_prime_UTR_variant	Exon 7 of 7		NP_001139133.1
GATA2	NM_001145662.1	c.*482C>T		3_prime_UTR_variant	Exon 6 of 6		NP_001139134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7	c.*482C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_032638.5	ENSP00000345681.2

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26494 AN: 152006 Hom.: 2467 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0549

Gnomad SAS AF: 0.0728

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.164 AC: 16278 AN: 99250 Hom.: 1475 Cov.: 0 AF XY: 0.165 AC XY: 7685 AN XY: 46594

African (AFR) AF: 0.163 AC: 709 AN: 4358

American (AMR) AF: 0.139 AC: 433 AN: 3124

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 723 AN: 5614

East Asian (EAS) AF: 0.0514 AC: 651 AN: 12656

South Asian (SAS) AF: 0.0904 AC: 85 AN: 940

European-Finnish (FIN) AF: 0.157 AC: 311 AN: 1982

Middle Eastern (MID) AF: 0.187 AC: 108 AN: 578

European-Non Finnish (NFE) AF: 0.190 AC: 11837 AN: 62254

Other (OTH) AF: 0.183 AC: 1421 AN: 7744

GnomAD4 genome AF: 0.174 AC: 26509 AN: 152124 Hom.: 2468 Cov.: 33 AF XY: 0.171 AC XY: 12738 AN XY: 74378

African (AFR) AF: 0.172 AC: 7156 AN: 41496

American (AMR) AF: 0.156 AC: 2394 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3472

East Asian (EAS) AF: 0.0549 AC: 284 AN: 5176

South Asian (SAS) AF: 0.0737 AC: 355 AN: 4818

European-Finnish (FIN) AF: 0.194 AC: 2057 AN: 10600

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13239 AN: 67942

Other (OTH) AF: 0.179 AC: 378 AN: 2116

Alfa AF: 0.187 Hom.: 7020

Bravo AF: 0.174

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Deafness-lymphedema-leukemia syndrome;C3280030:Monocytopenia with susceptibility to infections Benign:1

Feb 11, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Deafness-lymphedema-leukemia syndrome Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.1
DANN	Benign	0.74
PhyloP100		0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3803; hg19: chr3-128199380;