Genetic Variant NM_001145661.2:c.1431C>T (chr3-128481031-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001145661.2(GATA2):c.1431C>T(p.Thr477Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,577,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

GATA2
NM_001145661.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.637

Publications

0 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: 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

GATA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 3-128481031-G-A is Benign according to our data. Variant chr3-128481031-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 412746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.637 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.000138 (197/1425638) while in subpopulation AMR AF = 0.000584 (25/42786). AF 95% confidence interval is 0.000406. There are 0 homozygotes in GnomAdExome4. There are 92 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 7 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	HGVSp	Effect	Exon Rank	Protein
GATA2	NM_001145661.2	MANE Plus Clinical	c.1431C>T	p.Thr477Thr	synonymous	Exon 7 of 7	NP_001139133.1
GATA2	NM_032638.5	MANE Select	c.1431C>T	p.Thr477Thr	synonymous	Exon 6 of 6	NP_116027.2
GATA2	NM_001145662.1		c.1389C>T	p.Thr463Thr	synonymous	Exon 6 of 6	NP_001139134.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GATA2	ENST00000341105.7	TSL:1 MANE Select	c.1431C>T	p.Thr477Thr	synonymous	Exon 6 of 6	ENSP00000345681.2
GATA2	ENST00000487848.6	TSL:1 MANE Plus Clinical	c.1431C>T	p.Thr477Thr	synonymous	Exon 7 of 7	ENSP00000417074.1
GATA2	ENST00000430265.6	TSL:1	c.1389C>T	p.Thr463Thr	synonymous	Exon 6 of 6	ENSP00000400259.2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000158

AC:

AN:

221912

AF XY:

0.000135

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000644

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000277

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000795

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000138

AC:

197

AN:

1425638

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

703744

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32968

American (AMR)

AF:

0.000584

AC:

AN:

42786

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23596

East Asian (EAS)

AF:

0.000153

AC:

AN:

39306

South Asian (SAS)

AF:

0.0000379

AC:

AN:

79192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51840

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5082

European-Non Finnish (NFE)

AF:

0.000143

AC:

156

AN:

1092026

Other (OTH)

AF:

0.000119

AC:

AN:

58842

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41464

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000192

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000911

Hom.:

Bravo

AF:

0.000106

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

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

Hereditary cancer-predisposing syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.7

(source)

DANN

Benign

0.69

PhyloP100

-0.64

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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