rs760230147

Variant names:

• chr3-128486376-CAAAG-C
• rs760230147
• NM_001145661.2:c.230-12_230-9delCTTT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_032638.5(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_032638.5 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:2
• Conservation: PhyloP100: 0.198
• Publications: 0 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: 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

ACMG classification

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.

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.230-12_230-9delCTTT		intron	N/A	NP_001139133.1	P23769-1
	GATA2	NM_032638.5	MANE Select	c.230-12_230-9delCTTT		intron	N/A	NP_116027.2
	GATA2	NM_001145662.1		c.230-12_230-9delCTTT		intron	N/A	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.230-12_230-9delCTTT		intron	N/A	ENSP00000345681.2	P23769-1
	GATA2	ENST00000487848.6	TSL:1 MANE Plus Clinical	c.230-12_230-9delCTTT		intron	N/A	ENSP00000417074.1	P23769-1
	GATA2	ENST00000430265.6	TSL:1	c.230-12_230-9delCTTT		intron	N/A	ENSP00000400259.2	P23769-2

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 151952 Hom.: 0 Cov.: 32

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: 47 AN: 217586 AF XY: 0.000184

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.: 0 AF XY: 0.000309 AC XY: 222 AN XY: 718046

African (AFR) AF: 0.0000299 AC: 1 AN: 33390

American (AMR) AF: 0.00 AC: 0 AN: 43278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25756

East Asian (EAS) AF: 0.00 AC: 0 AN: 39398

South Asian (SAS) AF: 0.00 AC: 0 AN: 83802

European-Finnish (FIN) AF: 0.000378 AC: 17 AN: 44926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4736

European-Non Finnish (NFE) AF: 0.000425 AC: 471 AN: 1109392

Other (OTH) AF: 0.000150 AC: 9 AN: 59972

GnomAD4 genome AF: 0.000237 AC: 36 AN: 152070 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74322

African (AFR) AF: 0.0000723 AC: 3 AN: 41480

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2102

Alfa AF: 0.000434 Hom.: 0

Bravo AF: 0.000208

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	not specified (2)
-	-	1	Deafness-lymphedema-leukemia syndrome;C3280030:Monocytopenia with susceptibility to infections (1)
-	1	-	Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs760230147; hg19: chr3-128205219;