chr3-128480304-C-T

Variant names:

• chr3-128480304-C-T
• rs73203415
• NM_001145661.2:c.*715G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_032638.5(GATA2):​c.*715G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 233,388 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (62 hom., cov: 33)
  • Exomes 𝑓: 0.025 (45 hom.)
• Consequence: GATA2 NM_032638.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.102
• Publications: 4 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: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• 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: Ambry Genetics, Orphanet
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 3-128480304-C-T is Benign according to our data. Variant chr3-128480304-C-T is described in ClinVar as Benign. ClinVar VariationId is 343117.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0189 (2883/152342) while in subpopulation NFE AF = 0.0261 (1776/68030). AF 95% confidence interval is 0.0251. There are 62 homozygotes in GnomAd4. There are 1382 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2883 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032638.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA2	NM_001145661.2	MANE Plus Clinical	c.*715G>A		3_prime_UTR	Exon 7 of 7	NP_001139133.1	P23769-1
	GATA2	NM_032638.5	MANE Select	c.*715G>A		3_prime_UTR	Exon 6 of 6	NP_116027.2
	GATA2	NM_001145662.1		c.*715G>A		3_prime_UTR	Exon 6 of 6	NP_001139134.1	P23769-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA2	ENST00000341105.7	TSL:1 MANE Select	c.*715G>A		3_prime_UTR	Exon 6 of 6	ENSP00000345681.2	P23769-1
	GATA2	ENST00000487848.6	TSL:1 MANE Plus Clinical	c.*715G>A		3_prime_UTR	Exon 7 of 7	ENSP00000417074.1	P23769-1
	GATA2	ENST00000430265.6	TSL:1	c.*715G>A		3_prime_UTR	Exon 6 of 6	ENSP00000400259.2	P23769-2

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2884 AN: 152224 Hom.: 62 Cov.: 33

Gnomad AFR AF: 0.00494

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0261

Gnomad OTH AF: 0.0296

GnomAD4 exome AF: 0.0249 AC: 2021 AN: 81046 Hom.: 45 Cov.: 0 AF XY: 0.0261 AC XY: 973 AN XY: 37264

African (AFR) AF: 0.00385 AC: 15 AN: 3900

American (AMR) AF: 0.0252 AC: 63 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.0625 AC: 320 AN: 5124

East Asian (EAS) AF: 0.0000876 AC: 1 AN: 11414

South Asian (SAS) AF: 0.00855 AC: 6 AN: 702

European-Finnish (FIN) AF: 0.0161 AC: 1 AN: 62

Middle Eastern (MID) AF: 0.0589 AC: 29 AN: 492

European-Non Finnish (NFE) AF: 0.0281 AC: 1408 AN: 50078

Other (OTH) AF: 0.0263 AC: 178 AN: 6774

GnomAD4 genome AF: 0.0189 AC: 2883 AN: 152342 Hom.: 62 Cov.: 33 AF XY: 0.0186 AC XY: 1382 AN XY: 74490

African (AFR) AF: 0.00493 AC: 205 AN: 41590

American (AMR) AF: 0.0217 AC: 332 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0585 AC: 203 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00622 AC: 30 AN: 4826

European-Finnish (FIN) AF: 0.0190 AC: 202 AN: 10608

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0261 AC: 1776 AN: 68030

Other (OTH) AF: 0.0293 AC: 62 AN: 2116

Alfa AF: 0.0263 Hom.: 114

Bravo AF: 0.0195

Asia WGS AF: 0.00577 AC: 21 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Deafness-lymphedema-leukemia syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.6
DANN	Benign	0.84
PhyloP100		-0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs73203415; hg19: chr3-128199147;