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LYFE SCIENCES
Project: HERA
NM_007194.4:c.906A>C
p.Glu302Asp  ·  CHEK2
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Classification rationale
1

The CHEK2 c.906A>C (p.Glu302Asp, p.E302D) variant has not been observed in COSMIC and has been reported in ClinVar as a variant of uncertain significance.

clinvar ↗
2

This variant is present at low frequency in population databases, with gnomAD v2.1 total allele frequency 0.00342% (8/234112) and gnomAD v4.1 total allele frequency 0.00097% (14/1437854); the highest observed subpopulation frequency is 0.03471% (2/5762) in Middle Eastern individuals, which remains below a 0.1% rarity threshold.

gnomad_v2 ↗ gnomad_v4 ↗
3

In silico data do not show a consistent damaging signal: SpliceAI predicts no significant splice impact with a maximum delta score of 0.01, REVEL is 0.41, and BayesDel is 0.0235302.

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 v2.1This variant is present in gnomAD v2.1 (AF= 3.41717e-05; MAF= 0.00342%, 8/234112 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 6.68494e-05; MAF= 0.00668%, 2/29918 alleles, homozygotes = 0); grpmax FAF= 2.242e-05.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 9.73673e-06; MAF= 0.00097%, 14/1437854 alleles, homozygotes = 1) and has highest observed frequency in the Middle Eastern population (AF= 0.000347102; MAF= 0.03471%, 2/5762 alleles, homozygotes = 1); grpmax FAF= 6.098e-05.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Uncertain significance (12 clinical laboratories).
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. CHEK2, an intracellular kinase involved in control of the cell cycle, is altered in various cancer types.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.41. BayesDel score = 0.0235302.
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.
ResidueE302
Hotspots ↗