Genetic Variant NM_001145661.2:c.629_631dupGCG (chr3-128485966-A-ACGC) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PM4_Supporting

The NM_001145661.2(GATA2):c.629_631dupGCG(p.Gly210dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. V211V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

GATA2
NM_001145661.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.257

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: 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_001145661.2. Strenght limited to Supporting due to length of the change: 1aa.

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	UniProt
GATA2	NM_001145661.2	MANE Plus Clinical	c.629_631dupGCG	p.Gly210dup	conservative_inframe_insertion	Exon 4 of 7	NP_001139133.1	P23769-1
GATA2	NM_032638.5	MANE Select	c.629_631dupGCG	p.Gly210dup	conservative_inframe_insertion	Exon 3 of 6	NP_116027.2
GATA2	NM_001145662.1		c.629_631dupGCG	p.Gly210dup	conservative_inframe_insertion	Exon 3 of 6	NP_001139134.1	P23769-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GATA2	ENST00000341105.7	TSL:1 MANE Select	c.629_631dupGCG	p.Gly210dup	conservative_inframe_insertion	Exon 3 of 6	ENSP00000345681.2	P23769-1
GATA2	ENST00000487848.6	TSL:1 MANE Plus Clinical	c.629_631dupGCG	p.Gly210dup	conservative_inframe_insertion	Exon 4 of 7	ENSP00000417074.1	P23769-1
GATA2	ENST00000430265.6	TSL:1	c.629_631dupGCG	p.Gly210dup	conservative_inframe_insertion	Exon 3 of 6	ENSP00000400259.2	P23769-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Acute myeloid leukemia (1)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.26

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over