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KMT2Ac.5031G>ALikely benign
Print report
Variant interpretation report

KMT2A c.5031G>A, p.(Glu1677=)

NM_005933.3:c.5031G>A NP_005924.2:p.(Glu1677=) View identifiers
Classification
Likely benign

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.

Likely benign.A likely benign classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About KMT2A

No gene-level summary was recorded for this case.

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: 0 Benign evidence criteria: 2
Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 2
BP6Supporting
BP6 · supporting

This variant has been classified as Likely benign by Labcorp Genetics (formerly Invitae), a reputable clinical diagnostic laboratory (ClinVar variation ID 1925883, SCV002959647, criteria provided, single submitter). The underlying evidence is not available for independent evaluation.

BP7Supporting
BP7 · supporting

This is a synonymous variant (p.Glu1677=) with SpliceAI predicting no impact on splicing (max delta score 0.00), consistent with no effect on the gene product.

Recorded classification: Likely benign

gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BP6 supporting, BP7 supporting; combination = 2 supporting benign, which maps to Likely Benign.

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
Not recorded

gnomAD v4.1 allele counts were not recorded for this variant.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

No listed criterion applied
gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗
SpliceAI score
0.000 maximum delta

Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP7 → SpliceAI ↗
ClinVar submissions
1 reported laboratory submissions

1 Likely benign. ClinVar API review status: criteria provided, single submitter.

Applied · BP6 → ClinVar ↗
Functional evidence
Statement recorded

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

No listed criterion applied OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported

This variant has not previously been reported in somatic cancers (COSMIC).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.

Context only
COSMIC ↗Cancer Hotspots ↗
For specialists

Technical detail

ACMG/AMP criteria under Not recorded, with the data and sources behind each one.

29 criteria with recorded statuses: 2 met · 18 not met · 0 not assessed · 9 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM3PM4PM5PM6PP1PP2PP3PP4PP5PS5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

NM_005933.3:c.5031G>A is a synonymous variant (p.Glu1677=) in KMT2A with no predicted effect on splicing (SpliceAI max delta score 0.00).

This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada in all populations.

This variant has been classified as Likely benign by a reputable clinical diagnostic laboratory (Labcorp Genetics/Invitae) in ClinVar (variation ID 1925883), though the underlying evidence is not publicly available for independent review.

Two supporting benign criteria are met: BP6 (reputable source classifies as benign) and BP7 (synonymous variant with no predicted splicing impact). No pathogenic criteria are met.

Based on the ACMG/AMP 2015 classification framework, a Likely benign classification is appropriate (2 supporting benign criteria, 0 pathogenic criteria).

Met · 2

BP6 SupportingThis variant has been classified as Likely benign by Labcorp Genetics (formerly Invitae), a reputable clinical diagnostic laboratory (ClinVar variation ID 1925883, SCV002959647, criteria provided, single submitter). The underlying evidence is not available for independent evaluation. Details ▾Hide ▴
Evidence considered
  • ClinVar classification: Likely benign by Labcorp Genetics (Invitae). Single submitter with criteria provided
  • the Sherloc classification framework paper (PMID:28492532) is cited as supporting methodology but does not directly reference this variant.
Still missing
  • Single submitter only
  • no expert panel review. Underlying individual-level evidence not publicly available.
Sources
clinvar ↗
BP7 SupportingThis is a synonymous variant (p.Glu1677=) with SpliceAI predicting no impact on splicing (max delta score 0.00), consistent with no effect on the gene product. Details ▾Hide ▴
Evidence considered
  • Synonymous variant p.Glu1677= (c.5031G>A). SpliceAI max delta score 0.00
  • predicting no donor gain
  • donor loss
  • acceptor gain
  • or acceptor loss within 500 bp.
Still missing
  • Nucleotide-level conservation data not explicitly evaluated
  • the second prong of BP7 (nucleotide not highly conserved) could not be independently verified.
Sources
spliceai ↗

Not met · 18 · evaluated, threshold not reached

PS2 No de novo evidence has been reported for this variant. Details ▾Hide ▴
Evidence considered
  • No de novo observations identified in ClinVar
  • literature
  • or population databases.
Still missing
  • No parental testing data available to assess de novo status.
PS3 No functional studies have been identified for this variant. Details ▾Hide ▴
Evidence considered
  • No in vitro or in vivo functional data found in literature or curated databases.
Still missing
  • No functional characterization of this synonymous variant has been performed.
PS4 No case-control or prevalence data are available to support enrichment of this variant in affected individuals. Details ▾Hide ▴
Evidence considered
  • Variant is absent from gnomAD but no affected cohort data exist for statistical comparison.
Still missing
  • No case-control studies or affected cohort prevalence data available.
PM1 This variant is not located in a statistically significant mutational hotspot or a critical functional domain with established pathogenic enrichment. Details ▾Hide ▴
Evidence considered
  • Cancer Hotspots analysis confirms the variant does not lie in a statistically significant hotspot residue.
PM2 Although absent from gnomAD v2.1, v4.1, and gnomAD-Canada, this is a synonymous variant with no predicted functional impact (SpliceAI max delta 0.00). PM2 is not appropriately applied to synonymous variants absent evidence of a functional consequence. Details ▾Hide ▴
Evidence considered
  • Absent from gnomAD v2.1
  • v4.1
  • and gnomAD-Canada v1.0. SpliceAI max delta 0.00 confirms no cryptic splicing effect.
Sources
gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗spliceai ↗
PM6 No de novo observation has been reported for this variant without confirmation of paternity and maternity. Details ▾Hide ▴
Evidence considered
  • No putative de novo reports identified in ClinVar or literature.
Still missing
  • No trio or parental testing data available.
PP1 No segregation data are available for this variant. Details ▾Hide ▴
Evidence considered
  • No family studies or cosegregation analyses identified.
Still missing
  • No family segregation data available.
PP3 SpliceAI predicts no splicing impact (max delta score 0.00). No deleterious in silico predictions are available for this synonymous variant. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta score 0.00
  • no REVEL or BayesDel scores available for synonymous position.
Sources
spliceai ↗
PP4 No phenotype or clinical data are available to assess whether the patient's presentation is specific for KMT2A-related disease. Details ▾Hide ▴
Evidence considered
  • No proband phenotype information available in the evidence packet.
Still missing
  • Proband phenotype data not provided.
PP5 ClinVar classification for this variant is Likely benign, not pathogenic. PP5 requires a reputable source to report the variant as pathogenic. Details ▾Hide ▴
Evidence considered
  • ClinVar variation ID 1925883: classification is Likely benign (Labcorp/Invitae
  • criteria provided
  • single submitter).
Sources
clinvar ↗
BA1 This variant is absent from gnomAD; allele frequency does not exceed the 1% BA1 threshold. Details ▾Hide ▴
Evidence considered
  • Absent from gnomAD v2.1 (AF=0)
  • v4.1 (AF=0)
  • and gnomAD-Canada v1.0 (AF=0).
Sources
gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗
BS1 This variant is absent from gnomAD; allele frequency does not exceed the 0.3% BS1 threshold. Details ▾Hide ▴
Evidence considered
  • Absent from gnomAD v2.1 (AF=0)
  • v4.1 (AF=0)
  • and gnomAD-Canada v1.0 (AF=0).
Sources
gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗
BS2 No data are available on observation of this variant in healthy adults with full penetrance expected at an early age. Details ▾Hide ▴
Evidence considered
  • No control cohort data or healthy adult observations available.
Still missing
  • No data on variant observation in healthy adult controls.
BS3 No functional studies demonstrating no deleterious effect have been identified for this variant. Details ▾Hide ▴
Evidence considered
  • No in vitro or in vivo functional assays assessing this variant's effect have been identified in the literature or curated databases.
Still missing
  • No functional characterization data available for this synonymous variant.
BS4 No segregation data are available to demonstrate lack of cosegregation with disease. Details ▾Hide ▴
Evidence considered
  • No family segregation data available.
Still missing
  • No family studies to assess cosegregation or lack thereof.
BP2 No data are available on whether this variant has been observed in trans with a pathogenic variant in KMT2A. Details ▾Hide ▴
Evidence considered
  • No phase information or compound heterozygous observations available.
Still missing
  • No data on co-occurrence in trans with a pathogenic variant.
BP4 BP7 is the more specific ACMG/AMP criterion for synonymous variants with no predicted splicing impact. Applying both BP4 and BP7 would double-count the same SpliceAI evidence. BP7 is applied instead. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta 0.00 predicts no splicing impact
  • this evidence is captured under BP7 rather than BP4 to avoid double-counting.
Sources
spliceai ↗
BP5 No observation of this variant in a case with an alternate molecular basis for disease has been reported. Details ▾Hide ▴
Evidence considered
  • No cases identified where this variant was found alongside a different confirmed molecular cause for the phenotype.
Still missing
  • No data on alternate molecular diagnoses in carriers.
Not applicable · 9· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ASynonymous variant (p.Glu1677=) with no predicted splicing impact; PVS1 applies only to null variants (nonsense, frameshift, canonical ±1,2 splice, initiation codon, or exon deletion). Details ▾Hide ▴
Evidence considered
  • Variant is synonymous (p.Glu1677=)
  • SpliceAI max delta 0.00 confirms no cryptic splice effect. PVS1 decision framework confirms variant does not qualify for any PVS1 strength level.
Sources
pvs1_variant_assessmentpvs1_generic_framework ↗
PS1 N/ASynonymous variant with no amino acid change; PS1 requires a different nucleotide substitution at the same codon producing the same missense change, which is not applicable to synonymous variants. Details ▾Hide ▴
Evidence considered
  • Variant is synonymous (p.Glu1677=)
  • no amino acid change to support a PS1 comparator.
PM3 N/ASkipped per user instruction. Details ▾Hide ▴

No further detail was recorded.

PM4 N/ASkipped per user instruction. Additionally, this variant is a single nucleotide synonymous substitution, not an in-frame deletion/insertion or stop-loss. Details ▾Hide ▴

No further detail was recorded.

PM5 N/ASynonymous variant (p.Glu1677=) produces no amino acid change; PM5 requires a different pathogenic missense change at the same residue, which is not applicable to synonymous variants. Details ▾Hide ▴
Evidence considered
  • Variant is synonymous
  • no amino acid residue to compare. PM5 candidate harvesting was skipped: unable to parse missense residue context from normalized protein consequence.
Sources
pm5_candidates
PP2 N/ASynonymous variant, not missense. PP2 applies specifically to missense variants in genes where missense variants are a common mechanism of disease and benign missense variation is rare. Details ▾Hide ▴
Evidence considered
  • Variant is synonymous (p.Glu1677=)
  • not a missense change.
BP1 N/ASynonymous variant, not missense. BP1 applies specifically to missense variants in genes where primarily truncating variants cause disease. BP7 is the specific criterion for synonymous variants. Details ▾Hide ▴
Evidence considered
  • Variant is synonymous (p.Glu1677=)
  • not a missense change.
BP3 N/AIn-frame deletions/insertions in repetitive regions are not applicable; this is a single nucleotide synonymous substitution. Details ▾Hide ▴

No further detail was recorded.

PS5 N/ANot a standard ACMG/AMP 2015 criterion; no applicable evidence to assess under this category. Details ▾Hide ▴

No further detail was recorded.

Identifiers

Gene
KMT2A
Transcript
NM_005933.3
Coding (HGVS c.)
NM_005933.3:c.5031G>A
Protein (HGVS p.)
NP_005924.2:p.(Glu1677=)
GRCh38
chr11:118493092 G>A
GRCh37
chr11:118363807 G>A
ClinVar
1925883

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…
gnomAD v4.1 Allele count data not recorded
gnomAD v2.1 Allele count data not recorded
gnomAD-Canada v1.0 Allele count data not recorded

Statements

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

Pangolin splice lossmagnitude shown
-0.000
Pangolin splice gain
0.010

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

BP7 SupportingThis is a synonymous variant (p.Glu1677=) with SpliceAI predicting no impact on splicing (max delta score 0.00), consistent with no effect on the gene product. Details ▾Hide ▴
Evidence considered
  • Synonymous variant p.Glu1677= (c.5031G>A). SpliceAI max delta score 0.00
  • predicting no donor gain
  • donor loss
  • acceptor gain
  • or acceptor loss within 500 bp.
Still missing
  • Nucleotide-level conservation data not explicitly evaluated
  • the second prong of BP7 (nucleotide not highly conserved) could not be independently verified.
Sources
spliceai ↗
PP3 SpliceAI predicts no splicing impact (max delta score 0.00). No deleterious in silico predictions are available for this synonymous variant. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta score 0.00
  • no REVEL or BayesDel scores available for synonymous position.
Sources
spliceai ↗
BP4 BP7 is the more specific ACMG/AMP criterion for synonymous variants with no predicted splicing impact. Applying both BP4 and BP7 would double-count the same SpliceAI evidence. BP7 is applied instead. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta 0.00 predicts no splicing impact
  • this evidence is captured under BP7 rather than BP4 to avoid double-counting.
Sources
spliceai ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

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

  • Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.
    Nykamp K et al. · 2017
    Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. This is a methodology paper describing a variant classification framework; it does not report on the specific variant NM_005933.3:c.5031G>A in KMT2A.
    Does not name this variant
    PMID 28492532 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 Captured gnomAD v4.1 source record Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Recorded maximum delta 0.000 Open source ↗
ClinVar 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

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Likely benign (1 clinical laboratory). (ClinVarID = 1925883)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

Functional

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

Somatic

This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.