Genetic Variant NM_001145661.2:c.*183C>T (chr3-128480836-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001145661.2(GATA2):c.*183C>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 0.004 in 660,414 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0042 ( 11 hom. )

Consequence

GATA2
NM_001145661.2 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.387

Publications

1 publications found

Variant links:

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: G2P, Labcorp Genetics (formerly Invitae), 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

GATA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 3-128480836-G-A is Benign according to our data. Variant chr3-128480836-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00322 (490/152354) while in subpopulation NFE AF = 0.00465 (316/68028). AF 95% confidence interval is 0.00422. There are 4 homozygotes in GnomAd4. There are 222 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 490 AD gene.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GATA2	NM_001145661.2	MANE Plus Clinical	c.*183C>T	3_prime_UTR	Exon 7 of 7	NP_001139133.1	P23769-1
GATA2	NM_032638.5	MANE Select	c.*183C>T	3_prime_UTR	Exon 6 of 6	NP_116027.2
GATA2	NM_001145662.1		c.*183C>T	3_prime_UTR	Exon 6 of 6	NP_001139134.1	P23769-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GATA2	ENST00000341105.7	TSL:1 MANE Select	c.*183C>T	3_prime_UTR	Exon 6 of 6	ENSP00000345681.2	P23769-1
GATA2	ENST00000487848.6	TSL:1 MANE Plus Clinical	c.*183C>T	3_prime_UTR	Exon 7 of 7	ENSP00000417074.1	P23769-1
GATA2	ENST00000430265.6	TSL:1	c.*183C>T	3_prime_UTR	Exon 6 of 6	ENSP00000400259.2	P23769-2

Frequencies

GnomAD3 genomes

AF:

0.00322

AC:

490

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000699

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00464

Gnomad OTH

AF:

0.00573

GnomAD4 exome

AF:

0.00423

AC:

2151

AN:

508060

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

1097

AN XY:

261172

show subpopulations

African (AFR)

AF:

0.000440

AC:

AN:

13626

American (AMR)

AF:

0.00291

AC:

AN:

16852

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

309

AN:

13748

East Asian (EAS)

AF:

0.00

AC:

AN:

30674

South Asian (SAS)

AF:

0.00214

AC:

AN:

38768

European-Finnish (FIN)

AF:

0.00115

AC:

AN:

34712

Middle Eastern (MID)

AF:

0.00571

AC:

AN:

2100

European-Non Finnish (NFE)

AF:

0.00458

AC:

1509

AN:

329782

Other (OTH)

AF:

0.00514

AC:

143

AN:

27798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

107

214

321

428

535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00322

AC:

490

AN:

152354

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

222

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.000697

AC:

AN:

41586

American (AMR)

AF:

0.00242

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00186

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000753

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00465

AC:

316

AN:

68028

Other (OTH)

AF:

0.00567

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00371

Hom.:

Bravo

AF:

0.00340

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Deafness-lymphedema-leukemia syndrome (1)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.51

(source)

DANN

Benign

0.46

PhyloP100

-0.39

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over