NM_032638.5:c.363C>T

Variant names:

• chr3-128486235-G-A
• rs1352824690
• NM_001145661.2:c.363C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_032638.5(GATA2):​c.363C>T​(p.Phe121Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000078 in 1,410,724 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000078 (0 hom.)
• Consequence: GATA2 NM_032638.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.29
• 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: 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

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 3-128486235-G-A is Benign according to our data. Variant chr3-128486235-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 472457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.29 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 11 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA2	NM_001145661.2	MANE Plus Clinical	c.363C>T	p.Phe121Phe	synonymous	Exon 4 of 7	NP_001139133.1
	GATA2	NM_032638.5	MANE Select	c.363C>T	p.Phe121Phe	synonymous	Exon 3 of 6	NP_116027.2
	GATA2	NM_001145662.1		c.363C>T	p.Phe121Phe	synonymous	Exon 3 of 6	NP_001139134.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA2	ENST00000341105.7	TSL:1 MANE Select	c.363C>T	p.Phe121Phe	synonymous	Exon 3 of 6	ENSP00000345681.2
	GATA2	ENST00000487848.6	TSL:1 MANE Plus Clinical	c.363C>T	p.Phe121Phe	synonymous	Exon 4 of 7	ENSP00000417074.1
	GATA2	ENST00000430265.6	TSL:1	c.363C>T	p.Phe121Phe	synonymous	Exon 3 of 6	ENSP00000400259.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000425 AC: 7 AN: 164890 AF XY: 0.0000568

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000239

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000155

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000780 AC: 11 AN: 1410724 Hom.: 0 Cov.: 36 AF XY: 0.0000115 AC XY: 8 AN XY: 696602

African (AFR) AF: 0.00 AC: 0 AN: 32876

American (AMR) AF: 0.000139 AC: 5 AN: 36098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25248

East Asian (EAS) AF: 0.00 AC: 0 AN: 37632

South Asian (SAS) AF: 0.00 AC: 0 AN: 80450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5572

European-Non Finnish (NFE) AF: 0.00000368 AC: 4 AN: 1085690

Other (OTH) AF: 0.0000342 AC: 2 AN: 58540

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inborn genetic diseases Benign:1

Aug 20, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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

Dec 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.86
PhyloP100		3.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs1352824690; hg19: chr3-128205078; COSMIC: COSV62003189; COSMIC: COSV62003189;