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FLT3c.1792_1793insCTACGTTGATTTCAGAGAATATGAUncertain significance
Print report
Variant interpretation report

FLT3 c.1792_1793insCTACGTTGATTTCAGAGAATATGA, p.(Glu598delinsAlaThrLeuIleSerGluAsnMetLys)

NM_004119.2:c.1792_1793insCTACGTTGATTTCAGAGAATATGA NP_004110.2:p.(Glu598delinsAlaThrLeuIleSerGluAsnMetLys) View identifiers
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.

About FLT3

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: 2 Benign evidence criteria: 0
Pathogenic criteria applied · 2
PM1Moderate
PM1 · moderate

This variant affects FLT3 residue E598 in the juxtamembrane domain, within the codon 589-599 cluster where 47 of 51 reported FLT3 internal tandem duplications were located; published studies show this region is a recurrent activating hotspot and this supports PM1.

PM2Moderate
PM2 · moderate

This variant is absent from gnomAD v2.1 and gnomAD v4.1, so the observed population frequency is 0 and is below the default PM2 threshold of 0.1%.

Benign criteria applied · 0

No benign criterion marked as applied in the recorded assessment.

Recorded classification: Uncertain significance

Generic ACMG/AMP 2015 final classification combination rules were used because no usable official VCEP/CSPEC or local custom gene-specific final-classification framework was available.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

No screenshot for this evidence
Computational predictions
Not recorded

No SpliceAI or REVEL score is recorded in the fields used for this tile.

No listed criterion applied
ClinVar submissions
Not recorded

A ClinVar laboratory submission summary was not recorded.

Context only ClinVar ↗
Functional evidence
Statement recorded

OncoKB classifies this variant as Likely Oncogenic; biological effect: Likely Gain-of-function.

No listed criterion applied OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
Not assessed

No COSMIC evidence statement is recorded in this case.

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.

28 criteria with recorded statuses: 2 met · 7 not met · 13 not assessed · 6 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM3PM4PM5PM6PP1PP2PP3PP4PP5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

The FLT3 c.1792_1793insCTACGTTGATTTCAGAGAATATGA (p.(Glu598delinsAlaThrLeuIleSerGluAsnMetLys)) variant has not been observed in somatic cancers in COSMIC and has not been reported in ClinVar; however, OncoKB classifies this specific variant as Likely Oncogenic with a likely gain-of-function effect.

This variant is absent from gnomAD v2.1 and gnomAD v4.1, with an observed population frequency of 0, which is below the 0.1% PM2 threshold.

Published studies show that FLT3 internal tandem duplication and related length mutations in the juxtamembrane region are activating, and codons 589-599 form a recurrent cluster; this supports the pathogenic relevance of the E598 region, although a direct functional assay for this exact variant was not identified.

SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.08.

Met · 2

PM1 ModerateThis variant affects FLT3 residue E598 in the juxtamembrane domain, within the codon 589-599 cluster where 47 of 51 reported FLT3 internal tandem duplications were located; published studies show this region is a recurrent activating hotspot and this supports PM1. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Evidence considered
  • Variant normalization gives p.(Glu598delinsAlaThrLeuIleSerGluAsnMetLys), placing the event at E598 in exon 14.
  • PMID:9737679 reported FLT3 ITDs clustered at codons 589-599 in the juxtamembrane domain and showed activating behavior.
  • OncoKB classified this variant as Likely Oncogenic with likely gain-of-function effect.
  • Cancer Hotspots did not show a resolved residue row and was marked for human review.
Sources
PMID:9737679 ↗PMID:11090077 ↗PMID:11756186 ↗oncokb ↗hotspots ↗PMID:12384447 ↗
PM2 ModerateThis variant is absent from gnomAD v2.1 and gnomAD v4.1, so the observed population frequency is 0 and is below the default PM2 threshold of 0.1%. Details ▾Hide ▴
Rule
Generic ACMG population threshold: PM2 when population frequency is below 0.1%
Evidence considered
  • Absent from gnomAD v2.1.
  • Absent from gnomAD v4.1.
Sources
gnomad_v2 ↗gnomad_v4 ↗

Not met · 7 · evaluated, threshold not reached

PS3 Published functional studies support gain-of-function for FLT3 internal tandem duplication and length mutations as a class, but no well-established functional study directly testing this specific p.(Glu598delinsAlaThrLeuIleSerGluAsnMetLys) variant was identified, so PS3 is not met. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Evidence considered
  • OncoKB classifies the variant as Likely Oncogenic with likely gain-of-function effect.
  • The screened literature supports oncogenicity of FLT3 ITD/length mutations in general rather than this exact variant.
Still missing
  • Variant-specific functional assay data using this exact insertion
Sources
oncokb ↗PMID:11090077 ↗PMID:11756186 ↗PMID:12384447 ↗PMID:9737679 ↗PMID:23631653 ↗
PP5 No pathogenic classification from a germline clinical laboratory source was identified; this variant is absent from ClinVar, so PP5 is not met. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Evidence considered
  • The variant is absent from ClinVar.
Sources
clinvar ↗
BA1 This variant is absent from gnomAD v2.1 and gnomAD v4.1, so the observed population frequency is 0 and is below the benign BA1 threshold of 1%. Details ▾Hide ▴
Rule
Generic ACMG population threshold: BA1 when population frequency is above 1%
Evidence considered
  • Absent from gnomAD v2.1.
  • Absent from gnomAD v4.1.
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS1 This variant is absent from gnomAD v2.1 and gnomAD v4.1, so the observed population frequency is 0 and is below the benign BS1 threshold of 0.3%. Details ▾Hide ▴
Rule
Generic ACMG population threshold: BS1 when population frequency is above 0.3%
Evidence considered
  • Absent from gnomAD v2.1.
  • Absent from gnomAD v4.1.
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS3 Available functional studies describe activating effects for FLT3 internal tandem duplication and length mutations rather than normal function for this specific variant, so BS3 is not met. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Evidence considered
  • OncoKB classifies this variant as Likely Oncogenic with likely gain-of-function effect.
  • The reviewed literature supports abnormal activation of FLT3 ITD/length mutations.
Sources
oncokb ↗PMID:11090077 ↗PMID:11756186 ↗PMID:12384447 ↗PMID:9737679 ↗PMID:23631653 ↗
BP3 Although this is an in-frame insertion/duplication, it lies in the FLT3 juxtamembrane region that has published evidence for recurrent activating mutations, so the benign BP3 criterion for repetitive regions without known function is not met. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Evidence considered
  • The variant affects the juxtamembrane codon 589-599 activating cluster.
Sources
PMID:9737679 ↗PMID:11090077 ↗PMID:11756186 ↗
BP6 No reputable germline source classified this variant as benign or likely benign, and the variant is absent from ClinVar, so BP6 is not met. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Evidence considered
  • The variant is absent from ClinVar.
Sources
clinvar ↗

Not assessed · 13 · no assessment recorded

PS2 No confirmed de novo data with verified maternity and paternity were identified, so PS2 cannot be assessed. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Still missing
  • Confirmed de novo testing with parental relationships established
PS4 No case-control or statistically enriched germline case series data were identified for this variant, so PS4 cannot be assessed. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Evidence considered
  • The variant was not found in ClinVar.
  • The variant was not found in COSMIC.
Still missing
  • Affected-versus-control enrichment data for this specific variant in a germline disease setting
Sources
clinvar ↗cosmic ↗
PM3 No recessive inheritance data or trans observations with another pathogenic variant were identified, so PM3 cannot be assessed. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Still missing
  • Phase data and recessive disease context
PM4 This is an in-frame protein length change, but the available evidence supports a recurrent activating juxtamembrane duplication mechanism rather than a clearly independent non-repeat PM4 mechanism, so PM4 was not separately applied. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Evidence considered
  • Mutalyzer normalized the insertion to c.1792_1793ins1770_1793, consistent with tandem duplication.
  • The event maps to the known juxtamembrane ITD cluster.
Still missing
  • Evidence supporting a distinct PM4 mechanism independent of the juxtamembrane hotspot evidence
Sources
prefetchPMID:9737679 ↗
PM6 No assumed de novo occurrence without full parental confirmation was identified, so PM6 cannot be assessed. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Still missing
  • De novo occurrence data
PP1 No segregation data were identified for this variant, so PP1 cannot be assessed. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Still missing
  • Pedigree-based segregation data
PP3 SpliceAI predicts no significant splice effect with a maximum delta score of 0.08, but no validated protein-level in silico framework was identified for this in-frame insertion/duplication, so PP3 was not applied. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Evidence considered
  • SpliceAI max delta score = 0.08.
Still missing
  • Established in-frame indel prediction framework applicable to this variant type
Sources
spliceai ↗
PP4 No patient phenotype or family history data were provided to establish a highly specific FLT3-associated germline presentation, so PP4 cannot be assessed. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Still missing
  • Clinical phenotype and family history
BS2 No evidence was identified showing this variant in healthy adult individuals in a context where full penetrance would be expected, so BS2 cannot be assessed. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Still missing
  • Observation in unaffected individuals with an appropriate penetrance model
BS4 No non-segregation data were identified for this variant, so BS4 cannot be assessed. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Still missing
  • Family studies demonstrating lack of segregation with disease
BP2 No phase data with another pathogenic variant were identified, so BP2 cannot be assessed. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Still missing
  • Phase information with another variant
BP4 SpliceAI predicts no significant splice effect with a maximum delta score of 0.08, but no established benign in silico framework was identified for interpreting this in-frame insertion/duplication at the protein level, so BP4 was not applied. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Evidence considered
  • SpliceAI max delta score = 0.08.
Still missing
  • Validated benign prediction framework for this in-frame indel type
Sources
spliceai ↗
BP5 No alternate molecular diagnosis explaining the phenotype was identified, so BP5 cannot be assessed. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Still missing
  • Clinical and molecular data demonstrating an alternate cause of disease
Not applicable · 6· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis in-frame insertion/duplication does not create a nonsense, frameshift, or canonical +/-1,2 splice variant, so the generic PVS1 loss-of-function framework does not apply despite gene-level evidence that FLT3 loss of function can be disease relevant. Details ▾Hide ▴
Rule
Generic ACMG/AMP PVS1 fallback via ClinGen SVI PVS1 recommendations (PMC6185798)
Evidence considered
  • FLT3 loss of function is considered eligible for generic PVS1 review at the gene level.
  • The variant-level PVS1 assessment classified this change outside the default null-variant buckets and set apply_generic_pvs1_framework to false.
Sources
pvs1_gene_contextpvs1_variant_assessmentpvs1_generic_framework ↗PMID:32581359 ↗PMID:37681415 ↗PMID:39822584 ↗PMID:40568716 ↗PMID:35671390 ↗
PS1 N/APS1 applies to a different nucleotide change causing the same established pathogenic amino acid substitution; this variant is an in-frame insertion/duplication rather than a single amino acid substitution, so PS1 is not applicable. Details ▾Hide ▴
Rule
ACMG/AMP 2015
PM5 N/APM5 applies to a novel missense change at a residue where another missense change is established as pathogenic; this variant is an in-frame insertion/duplication, so PM5 is not applicable. Details ▾Hide ▴
Rule
ACMG/AMP 2015
PP2 N/APP2 is a missense criterion and does not apply to this in-frame insertion/duplication. Details ▾Hide ▴
Rule
ACMG/AMP 2015
BP1 N/ABP1 is a missense criterion and does not apply to this in-frame insertion/duplication. Details ▾Hide ▴
Rule
ACMG/AMP 2015
BP7 N/ABP7 applies to synonymous or certain noncoding variants with no predicted splice impact; this coding in-frame insertion/duplication is not eligible for BP7. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Evidence considered
  • SpliceAI max delta score = 0.08.
Sources
spliceai ↗

Identifiers

Gene
FLT3
Transcript
NM_004119.2
Coding (HGVS c.)
NM_004119.2:c.1792_1793insCTACGTTGATTTCAGAGAATATGA
Protein (HGVS p.)
NP_004110.2:p.(Glu598delinsAlaThrLeuIleSerGluAsnMetLys)
GRCh38
chr13:28034126 T>TTCATATTCTCTGAAATCAACGTAG
GRCh37
chr13:28608263 T>TTCATATTCTCTGAAATCAACGTAG

Gene diagram

Every interpreted variant in FLT3, mapped onto the exon structure of NM_004119.2. Select a row to find it on the plot.

FLT3NM_004119.2
Fetching transcript structure from UCSC…
gnomAD v4.1 Allele count data not recorded
gnomAD v2.1 Allele count data not recorded

Statements

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

PP3 SpliceAI predicts no significant splice effect with a maximum delta score of 0.08, but no validated protein-level in silico framework was identified for this in-frame insertion/duplication, so PP3 was not applied. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Evidence considered
  • SpliceAI max delta score = 0.08.
Still missing
  • Established in-frame indel prediction framework applicable to this variant type
Sources
spliceai ↗
BP4 SpliceAI predicts no significant splice effect with a maximum delta score of 0.08, but no established benign in silico framework was identified for interpreting this in-frame insertion/duplication at the protein level, so BP4 was not applied. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Evidence considered
  • SpliceAI max delta score = 0.08.
Still missing
  • Validated benign prediction framework for this in-frame indel type
Sources
spliceai ↗
BP7 N/ABP7 applies to synonymous or certain noncoding variants with no predicted splice impact; this coding in-frame insertion/duplication is not eligible for BP7. Details ▾Hide ▴
Rule
ACMG/AMP 2015
Evidence considered
  • SpliceAI max delta score = 0.08.
Sources
spliceai ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.08).

0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.

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 Captured SpliceAI source record Open source ↗
ClinVar Captured ClinVar source record 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.

ClinVar

This variant is absent from ClinVar.

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.08).

Functional

OncoKB classifies this variant as Likely Oncogenic; biological effect: Likely Gain-of-function.

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.