rs760230147

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001145661.2(GATA2):c.230-12_230-9delCTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000334 in 1,596,720 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

GATA2
NM_001145661.2 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: 0.198

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 -9 ACMG points.

BP6

Variant 3-128486376-CAAAG-C is Benign according to our data. Variant chr3-128486376-CAAAG-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 412753.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000237 (36/152070) while in subpopulation NFE AF = 0.000485 (33/68004). AF 95% confidence interval is 0.000354. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 36 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
GATA2	NM_001145661.2 link	c.230-12_230-9delCTTT	intron_variant	Intron 3 of 6	ENST00000487848.6	NP_001139133.1
GATA2	NM_032638.5 link	c.230-12_230-9delCTTT	intron_variant	Intron 2 of 5	ENST00000341105.7	NP_116027.2
GATA2	NM_001145662.1 link	c.230-12_230-9delCTTT	intron_variant	Intron 2 of 5		NP_001139134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7 link	c.230-12_230-9delCTTT		intron_variant	Intron 2 of 5	1	NM_032638.5	ENSP00000345681.2
GATA2	ENST00000487848.6 link	c.230-12_230-9delCTTT		intron_variant	Intron 3 of 6	1	NM_001145661.2	ENSP00000417074.1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

151952

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000216

AC:

AN:

217586

AF XY:

0.000184

show subpopulations

Gnomad AFR exome

AF:

0.0000786

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000680

Gnomad NFE exome

AF:

0.000445

Gnomad OTH exome

AF:

0.000185

GnomAD4 exome

AF:

0.000345

AC:

498

AN:

1444650

Hom.:

AF XY:

0.000309

AC XY:

222

AN XY:

718046

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33390

American (AMR)

AF:

0.00

AC:

AN:

43278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25756

East Asian (EAS)

AF:

0.00

AC:

AN:

39398

South Asian (SAS)

AF:

0.00

AC:

AN:

83802

European-Finnish (FIN)

AF:

0.000378

AC:

AN:

44926

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4736

European-Non Finnish (NFE)

AF:

0.000425

AC:

471

AN:

1109392

Other (OTH)

AF:

0.000150

AC:

AN:

59972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

106

132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000237

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41480

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5136

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000485

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.000434

Hom.:

Bravo

AF:

0.000208

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:1

Sep 25, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: GATA2 c.230-12_230-9delCTTT alters nucleotides located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00022 in 217586 control chromosomes, predominantly at a frequency of 0.00045 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in GATA2 causing GATA2-Related Disorders, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.230-12_230-9delCTTT in individuals affected with GATA2-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 412753). Based on the evidence outlined above, the variant was classified as likely benign. -

Jan 25, 2021

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DNA sequence analysis of the GATA2 gene demonstrated a sequence change in intron 2, c.230-12_230-9del. This change does not appear to have been previously described in patients with GATA2-related disorders and has been described in the gnomAD database with a low population frequency of 0.02% (dbSNP rs780435066). This sequence change is not clearly predicted to have a deleterious effect on splicing based on in silico splice prediction programs. It is possible that this sequence change represents a benign sequence change in the GATA2 gene that has not been identified to date. The functional significance of this sequence change is not known at present and its contribution to this patient's disease phenotype cannot definitively be determined. -

Hereditary cancer-predisposing syndrome

Uncertain:1

Sep 03, 2021

Sema4, Sema4

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:curation

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.20

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over