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LYFE SCIENCES
Project: HERA
NM_001145661.1:c.856G>C
p.Ala286Pro  ·  GATA2
ACMG/AMP
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Classification rationale
1

The GATA2 c.856G>C (p.Ala286Pro) variant has been reported in ClinVar as a variant of uncertain significance with three clinical laboratory submissions.

clinvar ↗
2

This variant is absent from gnomAD v2.1 and is present only once in gnomAD v4.1 (AF 6.19681e-07; 1/1613734 alleles), which supports rarity in population databases.

gnomad_v2 ↗ gnomad_v4 ↗
3

Computational evidence does not strongly support either a damaging or benign effect: SpliceAI predicts no significant splice impact (max delta score 0.00), REVEL is 0.352, and BayesDel is -0.0703764.

spliceai ↗
Applied criteria
Met
Not met
Not assessed
N/A
Very strong
Strong
Moderate
Supporting
Pathogenic evidence
PVS
PVS1
PS
PS1
PS2
PS3
PS4
PM
PM1
PM2
PM3
PM4
PM5
PM6
PP
PP1
PP2
PP3
PP4
PP5
Benign evidence
BA
BA1
BS
BS1
BS2
BS3
BS4
BP
BP1
BP2
BP3
BP4
BP5
BP6
BP7
PVS1
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Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
  • —
Rule
—
Publications
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Research and evidence
gnomAD v2.1 evidence
v2.1
gnomAD v4.1 evidence
v4.1
01
Population
gnomAD v2.1Absent from gnomAD v2.1.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 6.19681e-07; MAF= 0.00006%, 1/1613734 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.47469e-07; MAF= 0.00008%, 1/1179984 alleles, homozygotes = 0).
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Uncertain significance (3 clinical laboratories). (ClinVarID = 934804)
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Unknown Oncogenic Effect
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. GATA2, a transcription factor, is recurrently mutated in hematological malignancies and various solid tumors.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.352. BayesDel score = -0.0703764.
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueA286
Hotspots ↗