KMT2A c.5518C>T, p.Pro1840Ser
NM_005933.3:c.5518C>T
COSM9177241
Population Frequency
0.00319%
Low Frequency
ClinVar Classification
Unknown
0 publications
REVEL Score
0.326
Uncertain (Low)
COSMIC Recurrence
1 occurrences
No Criteria Applied
Classification Evidence
Detailed Information
Genetic Information
Gene & Transcript Details
Gene
KMT2A
Transcript
NM_005933.4
Total Exons
36
Strand
Forward (+)
Reference Sequence
NC_000011.9
Alternative Transcripts
| ID | Status | Details |
|---|---|---|
| NM_005933.2 | Alternative | 36 exons | Forward |
| NM_005933.3 | Alternative | 36 exons | Forward |
Variant Details
HGVS Notation
NM_005933.3:c.5518C>T
Protein Change
P1840S
Location
Exon 19
(Exon 19 of 36)
5'
Exon Structure (36 total)
3'
Functional Consequence
Missense Variant
Related Variants
No evidence of other pathogenic variants at position 1840 in gene KMT2A
Alternate Identifiers
COSM9177241
Variant interpretation based on transcript NM_005933.4
Clinical Evidence
Global Frequency
0.00319%
Rare
Highest in Population
Ashkenazi Jewish
0.0399%
Low Frequency
Global: 0.00319%
Ashkenazi Jewish: 0.0399%
0%
0.0005%
0.001%
0.01%
0.05%
1%+
Allele Information
Total: 250742
Alt: 8
Homozygotes: 0
ACMG Criteria Applied
PM2
This variant is rare in the population (0.003190% MAF).
Classification
Unknown
Publications
0 publications
Clinical Statement
Functional Domain
Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain (0 mutations).
Related Variants in This Domain
No evidence of other pathogenic variants at position 1840 in gene KMT2A
Functional Studies
Summary
The variant KMT2A P1840S has not been functionally characterized in the provided sources.
Computational Evidence
Pathogenicity Predictions
REVEL Score
0.326
0.326
Likely Benign
0.0
Uncertain (Low)
0.2
Uncertain (Med)
0.5
Likely Pathogenic
0.75
REVEL scores ≥ 0.75 are considered strong evidence of pathogenicity (PP3)
Predictor Consensus
Unknown
PP3 Applied
No
VCEP Guidelines
Applied ACMG/AMP Criteria
PM2
PM2 (Moderate)
According to standard ACMG guidelines: 'PM2 – Absent from controls (or at extremely low frequency if recessive)'. The evidence for this variant shows: The variant has a minor allele frequency (MAF) of 0.00319% in gnomAD, indicating it is extremely rare. Therefore, this criterion meets the requirements because the variant is absent from controls or present at a very low frequency.
BP4
BP4 (Supporting)
According to standard ACMG guidelines: 'BP4 – Multiple lines of computational evidence suggest no impact'. The evidence for this variant shows: In silico predictions indicate a lack of consensus on pathogenicity, with a REVEL score of 0.33 and SpliceAI suggesting minimal impact on splicing. Therefore, this criterion meets the requirements because the computational evidence suggests no significant impact on gene function.