rs10934857

Variant names:

• chr3-128480819-G-A
• rs10934857
• NM_001145661.2:c.*200C>T

Variant summary

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

The NM_001145661.2(GATA2):​c.*200C>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 0.228 in 582,460 control chromosomes in the GnomAD database, including 16,277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4035 hom., cov: 33)
  • Exomes 𝑓: 0.23 (12242 hom.)
• Consequence: GATA2 NM_001145661.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.342
• Publications: 9 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=-0.83).
• BP6: Variant 3-128480819-G-A is Benign according to our data. Variant chr3-128480819-G-A is described in ClinVar as Benign. ClinVar VariationId is 343127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145661.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA2	NM_001145661.2	MANE Plus Clinical	c.*200C>T		3_prime_UTR	Exon 7 of 7	NP_001139133.1
	GATA2	NM_032638.5	MANE Select	c.*200C>T		3_prime_UTR	Exon 6 of 6	NP_116027.2
	GATA2	NM_001145662.1		c.*200C>T		3_prime_UTR	Exon 6 of 6	NP_001139134.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA2	ENST00000341105.7	TSL:1 MANE Select	c.*200C>T		3_prime_UTR	Exon 6 of 6	ENSP00000345681.2
	GATA2	ENST00000487848.6	TSL:1 MANE Plus Clinical	c.*200C>T		3_prime_UTR	Exon 7 of 7	ENSP00000417074.1
	GATA2	ENST00000430265.6	TSL:1	c.*200C>T		3_prime_UTR	Exon 6 of 6	ENSP00000400259.2

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34115 AN: 152064 Hom.: 4031 Cov.: 33

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.230 AC: 98915 AN: 430278 Hom.: 12242 Cov.: 5 AF XY: 0.225 AC XY: 49843 AN XY: 221842

African (AFR) AF: 0.190 AC: 2338 AN: 12328

American (AMR) AF: 0.238 AC: 3613 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 2871 AN: 12968

East Asian (EAS) AF: 0.131 AC: 3881 AN: 29668

South Asian (SAS) AF: 0.109 AC: 3397 AN: 31146

European-Finnish (FIN) AF: 0.222 AC: 7015 AN: 31660

Middle Eastern (MID) AF: 0.273 AC: 522 AN: 1914

European-Non Finnish (NFE) AF: 0.256 AC: 69250 AN: 270408

Other (OTH) AF: 0.241 AC: 6028 AN: 24978

GnomAD4 genome AF: 0.224 AC: 34132 AN: 152182 Hom.: 4035 Cov.: 33 AF XY: 0.221 AC XY: 16435 AN XY: 74390

African (AFR) AF: 0.192 AC: 7950 AN: 41514

American (AMR) AF: 0.232 AC: 3548 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 747 AN: 3472

East Asian (EAS) AF: 0.136 AC: 701 AN: 5170

South Asian (SAS) AF: 0.105 AC: 507 AN: 4826

European-Finnish (FIN) AF: 0.222 AC: 2346 AN: 10588

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17483 AN: 68000

Other (OTH) AF: 0.239 AC: 504 AN: 2112

Alfa AF: 0.248 Hom.: 2471

Bravo AF: 0.228

Asia WGS AF: 0.133 AC: 466 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Deafness-lymphedema-leukemia syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.53
DANN	Benign	0.59
PhyloP100		-0.34
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: rs10934857; hg19: chr3-128199662;