rs760230147
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_032638.5(GATA2):c.230-12_230-9del variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
NM_032638.5 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.198
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -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 id is 412753.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 36 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA2 | NM_001145661.2 | c.230-12_230-9del | splice_polypyrimidine_tract_variant, intron_variant | ENST00000487848.6 | |||
GATA2 | NM_032638.5 | c.230-12_230-9del | splice_polypyrimidine_tract_variant, intron_variant | ENST00000341105.7 | |||
GATA2 | NM_001145662.1 | c.230-12_230-9del | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA2 | ENST00000341105.7 | c.230-12_230-9del | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_032638.5 | P1 | |||
GATA2 | ENST00000487848.6 | c.230-12_230-9del | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001145661.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000237 AC: 36AN: 151952Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000216 AC: 47AN: 217586Hom.: 0 AF XY: 0.000184 AC XY: 22AN XY: 119510
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GnomAD4 exome AF: 0.000345 AC: 498AN: 1444650Hom.: 0 AF XY: 0.000309 AC XY: 222AN XY: 718046
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GnomAD4 genome AF: 0.000237 AC: 36AN: 152070Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74322
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 25, 2021 | 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
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Sep 03, 2021 | - - |
Deafness-lymphedema-leukemia syndrome;C3280030:Monocytopenia with susceptibility to infections Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at