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LYFE SCIENCES
Project: HERA
NM_005933.3:c.5518C>T
p.Pro1840Ser  ·  KMT2A
ACMG/AMP
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Legacy Engine
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Classification rationale
1

The KMT2A NM_005933.3:c.5518C>T (NP_005924.2:p.(Pro1840Ser)) variant has been reported in ClinVar as likely benign by two clinical laboratories, without expert panel review.

clinvar ↗
2

This variant is present in gnomAD v2.1 at 0.00319% (8/250,742 alleles) and in gnomAD v4.1 at 0.00260% (42/1,613,654 alleles), with highest observed Ashkenazi Jewish frequencies of 0.03986% and 0.07436%, respectively; these values are below the default 0.1% PM2 threshold and below the 0.3% BS1 threshold.

gnomad_v2 ↗ gnomad_v4 ↗
3

Computational evidence does not support a damaging effect: SpliceAI predicts no significant splice impact with a maximum delta score of 0.02, REVEL is 0.326, and BayesDel is -0.184716.

spliceai ↗
4

This variant has not been shown to lie in a statistically significant hotspot.

hotspots ↗
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= 3.19053e-05; MAF= 0.00319%, 8/250742 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.000398645; MAF= 0.03986%, 4/10034 alleles, homozygotes = 0); grpmax FAF= 2.93e-06.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 2.60279e-05; MAF= 0.00260%, 42/1613654 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.000743595; MAF= 0.07436%, 22/29586 alleles, homozygotes = 0); grpmax FAF= 5.42e-06.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Likely benign (2 clinical laboratories). (ClinVarID = 2165272)
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. KMT2A, a histone methyltransferase, is altered by mutation or deletion in various solid tumors, and by chromosomal rearrangement in various hematologi
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02). REVEL score = 0.326. BayesDel score = -0.184716.
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.
ResidueP1840
Hotspots ↗