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LYFE SCIENCES
Project: HERA
NM_002354.3:c.294C>G
p.Asp98Glu  ·  EPCAM
ACMG/AMP
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Classification rationale
1

The EPCAM c.294C>G (p.Asp98Glu; p.D98E) variant has not been identified in a statistically significant cancer hotspot and has been reported in ClinVar as a variant of uncertain significance from one clinical laboratory.

hotspots ↗ clinvar ↗
2

This variant is rare in population databases, with allele frequencies of 0.00040% in gnomAD v2.1 and 0.00037% in gnomAD v4.1, both below the 0.1% PM2 threshold, and no homozygotes were observed.

gnomad_v2 ↗ gnomad_v4 ↗
3

SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.03.

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
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Gaps remaining
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Rule
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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= 3.9764e-06; MAF= 0.00040%, 1/251484 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.79059e-06; MAF= 0.00088%, 1/113758 alleles, homozygotes = 0).
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 3.71728e-06; MAF= 0.00037%, 6/1614082 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 5.08463e-06; MAF= 0.00051%, 6/1180026 alleles, homozygotes = 0); grpmax FAF= 1.83e-06.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Uncertain significance (1 clinical laboratory).
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Unknown Oncogenic Effect
OncoKB has not reviewed this specific variant; no variant-level oncogenicity or biological effect is available. Gene-level context: EPCAM, a transmembrane glycoprotein, is overexpressed in various cancer types.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV55392660, n = 1 times).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueD98
Hotspots ↗