About KMT2A
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
KMT2A c.2684A>G, p.(Lys895Arg)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
The variant is extremely rare in large population databases. gnomAD v2.1 reports an allele frequency of 0.00283% (8/282,230 alleles; 0 homozygotes; grpmax FAF=2.867e-05) and gnomAD v4.1 reports 0.00415% (67/1,614,060 alleles; 0 homozygotes; grpmax FAF=4.264e-05). Both frequencies are well below the 0.1% threshold for PM2 under generic ACMG/AMP. The variant is absent from gnomAD-Canada.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence support a benign effect for this variant. REVEL predicts a benign score of 0.224 (threshold >0.5 for pathogenic). BayesDel predicts a benign score of -0.154507 (negative scores indicate benign). SpliceAI predicts no significant splice impact (max delta score = 0.02). All three independent in silico tools concordantly predict no damaging effect.
Recorded classification: Uncertain significance
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, BP4 supporting benign; combination = 1 supporting + 1 supporting benign, which maps to VUS.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
67 / 1,614,060 alleles
gnomAD v4.1: 67 / 1,614,060 alleles. Recorded AF 4.15102e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 2.83457e-05; MAF= 0.00283%, 8/282230 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 6.22248e-05; MAF= 0.00622%, 8/128566 alleles, homozygotes = 0); grpmax FAF= 2.867e-05.
SpliceAI score
0.020 maximum delta
Recorded SpliceAI maximum delta score: 0.020. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
2 reported laboratory submissions
1 Uncertain significance · 1 Likely benign.
Context only
ClinVar ↗
Functional evidence
Statement recorded
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
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
4 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV63290798, n = 4 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
26 criteria with recorded statuses: 2 met · 5 not met · 16 not assessed · 3 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_005933.3:c.2684A>G (p.Lys895Arg) is a missense variant in exon 3 of KMT2A, a gene associated with autosomal dominant Wiedemann-Steiner syndrome.
This variant is extremely rare in large population databases, with an allele frequency of 0.00283% in gnomAD v2.1 (8/282,230 alleles) and 0.00415% in gnomAD v4.1 (67/1,614,060 alleles), with no homozygotes observed. It is absent from gnomAD-Canada (PM2_Supporting).
Multiple lines of computational evidence predict a benign effect: REVEL score 0.224 (benign range), BayesDel score -0.154507 (benign), and SpliceAI predicts no splicing impact with a maximum delta score of 0.02 (BP4_Supporting).
This variant has been reported in ClinVar (Variation ID 1335086) with conflicting classifications: Uncertain significance by Invitae and Likely benign by CeGaT Center for Human Genetics Tuebingen. Neither submission reaches a definitive pathogenic or benign classification.
The only publication associated with ClinVar submissions (PMID 28492532, Sherloc classification framework) does not mention this specific variant; it was reviewed in full text and confirmed to be a methodology reference only.
This variant has been reported in COSMIC (COSV63290798) in 4 somatic cancer samples, but this does not constitute germline disease evidence.
Several potentially relevant publications were identified by exploratory literature search (de novo report, functional studies, cosegregation data, domain hotspot analysis) but none of the associated PMIDs are present in the case directory for verification; these criteria (PS2, PS3, PS4, PM1, PM6, PP1, BS3) remain not assessed pending full-text retrieval and verification.
Applying the generic ACMG/AMP 2015 combination rules (PMID 25741868): the criteria met are PM2_Supporting (pathogenic) and BP4_Supporting (benign). These are conflicting at the supporting level and are insufficient to reach a likely pathogenic or likely benign classification. The variant is classified as a Variant of Uncertain Significance (VUS).
No criteria match.
Met · 2
PM2 SupportingThe variant is extremely rare in large population databases. gnomAD v2.1 reports an allele frequency of 0.00283% (8/282,230 alleles; 0 homozygotes; grpmax FAF=2.867e-05) and gnomAD v4.1 reports 0.00415% (67/1,614,060 alleles; 0 homozygotes; grpmax FAF=4.264e-05). Both frequencies are well below the 0.1% threshold for PM2 under generic ACMG/AMP. The variant is absent from gnomAD-Canada. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF=0.00283% (8/282
- 230)
- 0 hom
- grpmax FAF=2.867e-05.
- gnomAD v4.1: AF=0.00415% (67/1
- 614
- 060)
- grpmax FAF=4.264e-05.
- gnomAD-Canada: absent.
Sources
BP4 SupportingMultiple lines of computational evidence support a benign effect for this variant. REVEL predicts a benign score of 0.224 (threshold >0.5 for pathogenic). BayesDel predicts a benign score of -0.154507 (negative scores indicate benign). SpliceAI predicts no significant splice impact (max delta score = 0.02). All three independent in silico tools concordantly predict no damaging effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.224 (benign).
- BayesDel: -0.154507 (benign).
- SpliceAI max delta: 0.02 (no splice impact).
Sources
Not met · 5 · evaluated, threshold not reached
PP3 Multiple in silico tools predict a benign effect for this variant. REVEL score is 0.224 (well below the typical 0.5 threshold for pathogenic prediction). BayesDel score is -0.154507 (negative scores indicate benign). SpliceAI predicts no significant splice impact (max delta score = 0.02). None of the computational predictors support a damaging effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.224 (benign range).
- BayesDel: -0.154507 (benign).
- SpliceAI max delta: 0.02 (no splice impact).
Sources
PP5 No reputable source has recently reported this variant as pathogenic. The ClinVar record (1335086) shows classifications of Uncertain significance (Invitae) and Likely benign (CeGaT). The only associated publication (PMID 28492532) is a methodology paper (Sherloc classification framework) that does not mention this specific variant — it was cited by Invitae as a general classification reference. Full-text review confirmed the variant is not discussed. Details ▾Hide ▴
Evidence considered
- ClinVar: 1 VUS (Invitae)
- 1 LB (CeGaT). No pathogenic classification.
- PMID 28492532 (Sherloc): methodology paper
- variant not mentioned in full text.
Sources
BA1 The variant is extremely rare in population databases, far below the 1% BA1 threshold. The highest observed subpopulation frequency is 0.01644% (Middle Eastern, gnomAD v4.1). The overall gnomAD v4.1 AF is 0.00415% and v2.1 AF is 0.00283%. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF=0.00283%
- max subpop AF=0.00622% (NFE).
- gnomAD v4.1: AF=0.00415%
- max subpop AF=0.01644% (Middle Eastern).
- All frequencies far below 1% BA1 threshold.
Sources
BS1 The variant frequency is far below the 0.3% BS1 threshold. The highest observed subpopulation frequency is 0.01644% (Middle Eastern, gnomAD v4.1). No population approaches the 0.3% threshold required for BS1. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 max subpop AF: 0.00622% (NFE).
- gnomAD v4.1 max subpop AF: 0.01644% (Middle Eastern).
- All frequencies far below 0.3% BS1 threshold.
Sources
BP6 No reputable source has reported this variant as definitively benign. While CeGaT Center for Human Genetics Tuebingen classified it as Likely benign (SCV002063013), and Invitae classified it as Uncertain significance (SCV002170738), neither classification reaches the 'benign' threshold required for BP6. A single Likely benign classification from a clinical laboratory, in the context of a conflicting VUS from another laboratory, does not meet the BP6 standard of a reputable source reporting the variant as benign. Details ▾Hide ▴
Evidence considered
- ClinVar: 1 VUS (Invitae)
- 1 LB (CeGaT).
- No submission classifies as definitively benign.
Sources
Not assessed · 16 · no assessment recorded
PS1 No evidence of a different nucleotide change at codon 895 previously established as pathogenic. PS1 requires a known pathogenic variant at the same amino acid position resulting from a different nucleotide substitution. Details ▾Hide ▴
Still missing
- No pathogenic comparator at the same codon identified in available databases.
PS2 Exploratory literature search returned a lead suggesting a de novo occurrence of this variant in a child with Wiedemann-Steiner syndrome (PMID 35123456), but this PMID is not present in the case publications directory and the full text cannot be verified. Without confirming the variant is mentioned in the source and that parentage was confirmed, PS2 cannot be applied. Details ▾Hide ▴
Evidence considered
- Unverifiable exploratory lead: PMID 35123456 (not in case directory).
Still missing
- Requires verified de novo observation with confirmed parentage (STR or equivalent).
- Exploratory PMID 35123456 needs full-text retrieval and verification.
PS3 Exploratory literature search returned a lead suggesting reduced H3K4 methyltransferase activity (~35% of wild-type) for p.Lys895Arg (PMID 34210987), and a conflicting study suggesting normal activity (PMID 34567890). Neither PMID is present in the case publications directory, and the claims cannot be verified. COSMIC reports 4 somatic occurrences but this does not constitute well-established functional evidence for germline pathogenicity. Details ▾Hide ▴
Evidence considered
- COSMIC: 4 somatic occurrences (COSV63290798).
- Unverifiable exploratory leads: PMIDs 34210987 and 34567890 (not in case directory).
Still missing
- Requires well-established functional studies demonstrating a damaging effect on the gene product.
- Exploratory PMIDs 34210987 and 34567890 need full-text retrieval and verification.
PS4 The variant prevalence in affected individuals versus the general population cannot be reliably determined from available data. ClinVar has only 2 submitters (Invitae: VUS; CeGaT: LB) and no proband counts are specified. An exploratory lead claimed 5 unrelated probands but the source cannot be verified. The gnomAD population frequency is extremely low (AF ~0.003-0.004%), which would support case-control comparison if affected counts were known. Details ▾Hide ▴
Evidence considered
- ClinVar: 2 submissions (1 VUS
- 1 LB)
- no proband counts.
- gnomAD: extremely rare (AF 0.00283% v2.1
- 0.00415% v4.1).
- Unverifiable exploratory lead claiming 5 probands.
Still missing
- Requires confirmed count of unrelated affected probands to perform case-control comparison against gnomAD.
Sources
PM1 Exploratory literature search suggested residue 895 lies within the PHD1 finger domain (residues 880-940), a known functional domain in KMT2A with enrichment of pathogenic missense variants (PMID 32165498). However, the cited PMID is not in the case publications directory and the domain hotspot status cannot be verified from available sources. The cancer hotspots analysis classified the residue as not statistically significant for somatic mutations, but this does not directly address germline domain-level constraint. Details ▾Hide ▴
Evidence considered
- Cancer Hotspots: residue not in a statistically significant hotspot.
- Unverifiable exploratory lead: PMID 32165498 regarding PHD1 domain enrichment.
Still missing
- Requires confirmation that codon 895 lies within a well-established mutational hotspot or critical functional domain without benign variation.
- Exploratory PMID 32165498 needs full-text retrieval.
PM6 Exploratory literature search returned a lead describing a de novo occurrence without confirmed parentage (PMID 35123456). This PMID is not present in the case publications directory and cannot be verified. Without a verified de novo observation, PM6 cannot be applied. Details ▾Hide ▴
Evidence considered
- Unverifiable exploratory lead: PMID 35123456 (not in case directory).
Still missing
- Requires verified de novo observation (without parentage confirmation for PM6
- with confirmation for upgrade to PS2).
- Exploratory PMID 35123456 needs full-text retrieval and verification.
PP1 Exploratory literature search returned a lead describing cosegregation of this variant with Wiedemann-Steiner syndrome in a family (3 meioses; PMID 32876543). This PMID is not present in the case publications directory and cannot be verified. Without confirmed cosegregation data, PP1 cannot be applied. Details ▾Hide ▴
Evidence considered
- Unverifiable exploratory lead: PMID 32876543 (not in case directory).
Still missing
- Requires verified cosegregation data in affected family members.
- Exploratory PMID 32876543 needs full-text retrieval and verification.
PP2 PP2 requires that the gene has a low rate of benign missense variation (high constraint) and that missense variants are a common disease mechanism. While KMT2A missense variants are a recognized cause of Wiedemann-Steiner syndrome, specific constraint metrics (e.g., missense Z-score, gnomAD o/e ratio) were not available in the evidence bundle for this gene. Cannot apply without these quantitative data. Details ▾Hide ▴
Evidence considered
- KMT2A is associated with autosomal dominant Wiedemann-Steiner syndrome
- both missense and truncating variants reported.
Still missing
- Requires gene-level missense constraint metrics (gnomAD missense Z-score or o/e ratio) to determine eligibility for PP2.
PP4 No detailed patient phenotype data are available in verifiable sources. The ClinVar submissions do not include condition labels or phenotype descriptions. PP4 requires that the patient's phenotype or family history is highly specific for a disease with a single genetic etiology. Details ▾Hide ▴
Evidence considered
- ClinVar submissions do not include detailed phenotype data.
Still missing
- Requires confirmed patient phenotype data highly specific for Wiedemann-Steiner syndrome.
BS2 No data available on observation of this variant in healthy adults without the associated phenotype. While gnomAD includes population controls, the disease (Wiedemann-Steiner syndrome) has variable expressivity and the health status of gnomAD individuals is unknown. BS2 requires confirmed observation in a healthy adult with full penetrance expected at an early age. Details ▾Hide ▴
Evidence considered
- gnomAD allele counts not informative for BS2 (health status unknown in population databases).
Still missing
- Requires confirmed observation in healthy adult(s) without Wiedemann-Steiner syndrome features.
BS3 Exploratory literature search returned a lead describing a functional assay where p.Lys895Arg retained normal H3K4 methyltransferase activity in HEK293T cells (PMID 34567890), which would support BS3. However, this conflicts with another exploratory lead showing reduced activity (PMID 34210987). Neither PMID is in the case publications directory, and the claims cannot be verified. Details ▾Hide ▴
Evidence considered
- Unverifiable exploratory leads with conflicting functional results: PMIDs 34210987 and 34567890 (not in case directory).
Still missing
- Requires well-established functional studies showing no damaging effect.
- Conflicting exploratory leads need resolution through full-text verification.
BS4 No data available demonstrating lack of segregation of this variant with disease in affected family members. BS4 requires that the variant does not segregate with disease in families (e.g., an affected relative does not carry the variant). Available cosegregation data (unverifiable exploratory lead, PMID 32876543) actually suggests the variant does segregate with disease. Details ▾Hide ▴
Evidence considered
- No verified non-segregation data available.
Still missing
- No family studies showing affected individuals without the variant.
BP1 BP1 applies to missense variants in genes where primarily truncating variants cause disease. KMT2A-related Wiedemann-Steiner syndrome is caused by both missense and truncating variants. The pvs1_gene_context literature identifies both variant types as disease-causing. Without evidence that the gene's disease mechanism is exclusive to truncating variants, BP1 cannot be applied. Details ▾Hide ▴
Evidence considered
- KMT2A Wiedemann-Steiner syndrome: both missense and truncating variants are established disease mechanisms
- BP1 not applicable.
Sources
pvs1_gene_context
BP2 No data available on observation of this variant in trans with a known pathogenic KMT2A variant in an unaffected individual. KMT2A-related disease is autosomal dominant, making such observations unlikely. BP2 is generally not applicable to dominant conditions unless a specific recessive or digenic model is demonstrated. Details ▾Hide ▴
Evidence considered
- No trans observation data available
- autosomal dominant condition.
BP5 No data available on observation of this variant in a case with an alternate molecular basis for disease. BP5 requires that the variant is found in a patient with a clear alternate genetic cause for their phenotype. Details ▾Hide ▴
Still missing
- Requires data on probands with this variant who also carry an alternate molecular diagnosis.
PS5 No evidence from a reputable source recently reporting this variant as pathogenic. The ClinVar submissions are VUS (Invitae) and Likely benign (CeGaT). No expert panel or guideline-based classification calling this variant pathogenic is available. Details ▾Hide ▴
Not applicable · 3· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis is a missense variant (c.2684A>G, p.Lys895Arg) and does not fall into any null-variant bucket (nonsense, frameshift, canonical ±1,2 splice consensus, initiation codon, or exon-level deletion). The pvs1_variant_assessment confirms variant_bucket='other' and apply_generic_pvs1_framework=false. Details ▾Hide ▴
Evidence considered
- Missense variant p.Lys895Arg — not a null variant
- generic PVS1 framework not applicable.
Sources
pvs1_variant_assessmentpvs1_gene_context
PM5 N/ANo pathogenic comparator variant at the same amino acid residue (Lys895) with a different amino acid change could be identified. The pm5_candidates.json returned no candidates and recommended against applying PM5. Details ▾Hide ▴
Evidence considered
- pm5_candidates.json: 0 same-residue candidates found.
Sources
pm5_candidates
BP7 N/AThis is a missense variant (c.2684A>G, p.Lys895Arg), not a synonymous variant. BP7 applies only to synonymous (silent) variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense variant — BP7 is for synonymous variants only.
Identifiers
- Gene
- KMT2A
- Transcript
- NM_005933.3
- Coding (HGVS c.)
- NM_005933.3:c.2684A>G
- Protein (HGVS p.)
- NP_005924.2:p.(Lys895Arg)
- GRCh38
- chr11:118473843 A>G
- GRCh37
- chr11:118344558 A>G
- ClinVar
- 1335086
- COSMIC
- COSV63290798
Gene diagram
Every interpreted variant in KMT2A, mapped onto the exon structure of NM_005933.3. Select a row to find it on the plot.
KMT2ANM_005933.3
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in KMT2A
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
67 / 1,614,060 alleles
AF 4.15e-05 · 0 homozygotes · FAF 4.26e-05
gnomAD v2.1
8 / 282,230 alleles
AF 2.83e-05 · 0 homozygotes · FAF 2.87e-05
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 4.2e-05 · 67 / 1,614,060 alleles · 0 hom · FAF 4.3e-05
| Middle Eastern1 / 6,084 | 0.00016 |
| European (non-Finnish)63 / 1,180,034 | 5.3e-05 |
| Remaining individuals3 / 62,490 | 4.8e-05 |
0 alternate alleles recorded in 7 other groups: Admixed American, European (Finnish), Amish, East Asian, South Asian, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 2.8e-05 · 8 / 282,230 alleles · 0 hom · FAF 2.9e-05
| European (non-Finnish)8 / 128,566 | 6.2e-05 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 4.15102e-05; MAF= 0.00415%, 67/1614060 alleles, homozygotes = 0) and has highest observed frequency in the Middle Eastern population (AF= 0.000164366; MAF= 0.01644%, 1/6084 alleles, homozygotes = 0); grpmax FAF= 4.264e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 2.83457e-05; MAF= 0.00283%, 8/282230 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 6.22248e-05; MAF= 0.00622%, 8/128566 alleles, homozygotes = 0); grpmax FAF= 2.867e-05.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.224
- BayesDel
- -0.155
How the predictions were used
BP4 SupportingMultiple lines of computational evidence support a benign effect for this variant. REVEL predicts a benign score of 0.224 (threshold >0.5 for pathogenic). BayesDel predicts a benign score of -0.154507 (negative scores indicate benign). SpliceAI predicts no significant splice impact (max delta score = 0.02). All three independent in silico tools concordantly predict no damaging effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.224 (benign).
- BayesDel: -0.154507 (benign).
- SpliceAI max delta: 0.02 (no splice impact).
Sources
PP3 Multiple in silico tools predict a benign effect for this variant. REVEL score is 0.224 (well below the typical 0.5 threshold for pathogenic prediction). BayesDel score is -0.154507 (negative scores indicate benign). SpliceAI predicts no significant splice impact (max delta score = 0.02). None of the computational predictors support a damaging effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.224 (benign range).
- BayesDel: -0.154507 (benign).
- SpliceAI max delta: 0.02 (no splice impact).
Sources
BP7 N/AThis is a missense variant (c.2684A>G, p.Lys895Arg), not a synonymous variant. BP7 applies only to synonymous (silent) variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense variant — BP7 is for synonymous variants only.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02). REVEL score = 0.224. BayesDel score = -0.154507.
1 paper record listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
-
PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Nykamp K et al. · 2017No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
67 / 1,614,060 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.020
Open source ↗
ClinVar
1 Uncertain significance · 1 Likely benign
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/1335086/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-118344558-A-G?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-118473843-A-G?dataset=g…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_005933.3%3Ac.2684…
- OncoKB ↗www.oncokb.org/gene/KMT2A/K895R
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=190464328
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 4.15102e-05; MAF= 0.00415%, 67/1614060 alleles, homozygotes = 0) and has highest observed frequency in the Middle Eastern population (AF= 0.000164366; MAF= 0.01644%, 1/6084 alleles, homozygotes = 0); grpmax FAF= 4.264e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 2.83457e-05; MAF= 0.00283%, 8/282230 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 6.22248e-05; MAF= 0.00622%, 8/128566 alleles, homozygotes = 0); grpmax FAF= 2.867e-05.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (1 clinical laboratory) and as Likely benign (1 clinical laboratory). (ClinVarID = 1335086)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02). REVEL score = 0.224. BayesDel score = -0.154507.
Functional
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
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV63290798, n = 4 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.