About U2AF1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
U2AF1 c.132+18del, p.?
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
PM2Moderate
PM2 · moderate
NM_006758.2:c.132+18del is absent from gnomAD v4.1 (0/6520 alleles, AF = 0.0%), gnomAD v2.1, and gnomAD-Canada. This is consistent with PM2: absent from population databases at a frequency below 0.1%.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
SpliceAI predicts no splice impact for NM_006758.2:c.132+18del (max delta score = 0.00). For an intronic variant, the relevant computational evidence is splice prediction, and the sole applicable in silico tool indicates no effect. Other in silico tools (REVEL, BayesDel) are not applicable to non-SNV variants.
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 moderate, BP4 supporting benign; combination = 1 moderate + 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
0 / 6,520 alleles
gnomAD v4.1: 0 / 6,520 alleles. Recorded AF 0. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Context only
ClinVar ↗
No screenshot for this evidence
Functional evidence
Not recorded
No standalone functional evidence summary is recorded in evidence_summary.functional.
No listed criterion applied
OncoKB ↗
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Context only
COSMIC ↗
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 · 17 not met · 0 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_006758.2:c.132+18del is an intronic deletion (intron 2, +18) in U2AF1. It is absent from gnomAD v4.1 (0/6520 alleles), meeting PM2 at moderate strength.
SpliceAI predicts no splice impact for this variant (max delta = 0.00), meeting BP4 at supporting benign strength.
PVS1 is not applicable: this intronic variant does not fall into any null-variant bucket (nonsense, frameshift, or canonical ±1,2 splice site) under ClinGen SVI PVS1 recommendations (PMC6185798). SpliceAI corroborates absence of splice effect.
The variant is absent from ClinVar, COSMIC, and the published literature. No functional studies, de novo reports, or segregation data are available.
With one moderate pathogenic criterion (PM2) and one supporting benign criterion (BP4), the evidence is conflicting and insufficient to classify as likely pathogenic or likely benign. The variant is classified as a Variant of Uncertain Significance (VUS) under generic ACMG/AMP 2015 rules.
No criteria match.
Met · 2
PM2 ModerateNM_006758.2:c.132+18del is absent from gnomAD v4.1 (0/6520 alleles, AF = 0.0%), gnomAD v2.1, and gnomAD-Canada. This is consistent with PM2: absent from population databases at a frequency below 0.1%. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 0/6520 alleles (AF = 0.0%)
- gnomAD v2.1: absent
- gnomAD-Canada v1.0: absent
Sources
BP4 SupportingSpliceAI predicts no splice impact for NM_006758.2:c.132+18del (max delta score = 0.00). For an intronic variant, the relevant computational evidence is splice prediction, and the sole applicable in silico tool indicates no effect. Other in silico tools (REVEL, BayesDel) are not applicable to non-SNV variants. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00 — no predicted donor gain
- donor loss
- acceptor gain
- or acceptor loss
- Pangolin scores: splice gain = 0.01
- splice loss = -0.05 (both near zero)
Sources
Not met · 17 · evaluated, threshold not reached
PS2 No de novo occurrence data are available for NM_006758.2:c.132+18del. No publications or database records report this variant as de novo with confirmed paternity and maternity. Details ▾Hide ▴
Evidence considered
- No de novo reports found in ClinVar
- literature
- or any evidence source
Still missing
- De novo status could not be assessed without proband/parental genotype data
PS3 No well-established in vitro or in vivo functional studies have been performed for NM_006758.2:c.132+18del. No functional data were identified in the literature or curated databases. Details ▾Hide ▴
Evidence considered
- No functional studies found for this variant in any evidence source
Still missing
- Functional characterization of this intronic variant has not been performed
PS4 No case-control or cohort data are available to assess whether the prevalence of NM_006758.2:c.132+18del is significantly increased in affected individuals versus controls. Details ▾Hide ▴
Evidence considered
- No affected-vs-control prevalence data available for this variant
Still missing
- Prevalence data in affected individuals are unavailable
PM1 NM_006758.2:c.132+18del is located in intron 2 (+18), which is not within a characterized mutational hotspot or critical functional domain of U2AF1. Known U2AF1 hotspots are at residues S34 and Q157 within the coding region. Details ▾Hide ▴
Evidence considered
- Variant is intronic (+18)
- not in a known U2AF1 functional domain or hotspot
- Hotspot analysis: residue_significant = false
- exact_variant_listed = no
PM6 No assumed de novo occurrence (without confirmation of paternity/maternity) has been reported for NM_006758.2:c.132+18del in any database or publication. Details ▾Hide ▴
Evidence considered
- No de novo reports found in any evidence source
Still missing
- De novo status cannot be assessed without proband/parental genotype data
PP1 No cosegregation data are available for NM_006758.2:c.132+18del. Family studies have not been reported. Details ▾Hide ▴
Evidence considered
- No cosegregation data available
Still missing
- Family segregation studies have not been performed
PP3 No computational evidence supports a deleterious effect. SpliceAI predicts no splice impact (max delta score = 0.00). REVEL and BayesDel are not applicable to non-SNV variants. No in silico tools predict pathogenicity for this intronic deletion. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00 — no splice alteration predicted
- REVEL not applicable (not SNV)
- BayesDel not applicable (not SNV)
Sources
PP4 No patient phenotype or family history data are available to assess whether the proband's clinical presentation is specific for a U2AF1-related disorder. Details ▾Hide ▴
Evidence considered
- No proband phenotype data available
Still missing
- Proband phenotype and family history are not available for review
PP5 NM_006758.2:c.132+18del is absent from ClinVar. No reputable source has reported this variant as pathogenic. Details ▾Hide ▴
BA1 NM_006758.2:c.132+18del is absent from gnomAD v4.1 (0/6520 alleles, AF = 0.0%). The allele frequency does not exceed the BA1 threshold of >1% in any population. The highest subpopulation frequency is 0.0% in all groups. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 AF = 0.0% across all populations
- Highest subpopulation AF = 0.0% (AFR
- NFE
- EAS
- etc.)
Sources
BS1 NM_006758.2:c.132+18del is absent from gnomAD (0/6520 alleles, AF = 0.0%). The allele frequency does not exceed the BS1 threshold of >0.3% (non-VCEP cutoff). Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 AF = 0.0% — does not meet BS1 >0.3% threshold
Sources
BS2 No data are available regarding observation of NM_006758.2:c.132+18del in healthy adults with full penetrance expected at an early age. Details ▾Hide ▴
Evidence considered
- No healthy adult observation data available
Still missing
- Population data do not include phenotype correlation
BS3 No well-established in vitro or in vivo functional studies have been performed demonstrating no damaging effect for NM_006758.2:c.132+18del. While SpliceAI predicts no splice impact, this alone is insufficient to meet BS3 which requires experimental functional evidence. Details ▾Hide ▴
Evidence considered
- SpliceAI delta = 0.00 suggests no splice effect
- but BS3 requires experimental functional data
- not in silico prediction alone
Still missing
- Experimental functional studies (e.g.
- RNA analysis
- minigene assay) have not been performed
Sources
BS4 No cosegregation data are available to assess lack of segregation with disease for NM_006758.2:c.132+18del. Details ▾Hide ▴
Evidence considered
- No family segregation data available
Still missing
- Family studies have not been performed
BP2 No data are available regarding observation of NM_006758.2:c.132+18del in trans with a pathogenic variant in a fully penetrant recessive disorder, or in cis with a pathogenic variant in a dominant disorder. Details ▾Hide ▴
Evidence considered
- No phase or co-occurrence data available
Still missing
- Phase information is unavailable
BP5 No alternative molecular basis for disease has been identified in the proband that would explain the phenotype independent of NM_006758.2:c.132+18del. Details ▾Hide ▴
Evidence considered
- No alternative molecular diagnosis data available
Still missing
- Proband genetic workup data are unavailable
BP6 NM_006758.2:c.132+18del is absent from ClinVar. No reputable source has reported this variant as benign. Details ▾Hide ▴
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_006758.2:c.132+18del is an intronic deletion at position +18 of intron 2. It is not a null variant (nonsense, frameshift, initiation codon, or canonical ±1,2 splice site) and therefore does not meet PVS1 criteria under generic ACMG/AMP or ClinGen SVI PVS1 recommendations (PMC6185798). SpliceAI predicts no splice impact (max delta = 0.00). Details ▾Hide ▴
Evidence considered
- Variant is intronic (+18)
- not a canonical splice site variant
- SpliceAI max delta score = 0.00
- no predicted splice alteration
- PVS1 variant assessment classifies as 'other' bucket
- apply_generic_pvs1_framework = false
Sources
PS1 N/APS1 requires the same amino acid change as a previously established pathogenic variant. NM_006758.2:c.132+18del is an intronic deletion that does not alter the amino acid sequence; no protein consequence is defined. Details ▾Hide ▴
Evidence considered
- Intronic variant with no predictable amino acid change
PM3 N/ASkipped per adjudication instructions. Details ▾Hide ▴
No further detail was recorded.
PM4 N/APM4 applies to protein length changes due to in-frame deletions/insertions or stop-loss variants. NM_006758.2:c.132+18del is an intronic deletion that does not alter protein length or coding sequence. Details ▾Hide ▴
Evidence considered
- Intronic variant
- no protein length alteration
PM5 N/APM5 requires a novel missense variant at the same amino acid residue as a known pathogenic missense variant. NM_006758.2:c.132+18del is an intronic deletion, not a missense variant. Protein consequence is undefined (p.?). Details ▾Hide ▴
Evidence considered
- Intronic variant
- not a missense change
- PM5 candidate harvesting was not applicable: protein consequence is p.?
- pm5_mode = unknown
- eligible_for_classic_pm5_search = false
Sources
pm5_candidates
PP2 N/APP2 applies to missense variants in a gene with a low rate of benign missense variation and where missense is a common disease mechanism. NM_006758.2:c.132+18del is an intronic deletion, not a missense variant. Details ▾Hide ▴
Evidence considered
- Intronic variant
- not a missense change
BP1 N/ABP1 applies to missense variants in genes where truncating variants are the primary disease mechanism. NM_006758.2:c.132+18del is an intronic deletion, not a missense variant. Details ▾Hide ▴
Evidence considered
- Intronic variant
- not a missense change
BP3 N/ABP3 applies to in-frame deletions or insertions in repetitive regions without a known function. NM_006758.2:c.132+18del is an intronic deletion, not an in-frame coding indel. Details ▾Hide ▴
Evidence considered
- Intronic variant
- not an in-frame indel
BP7 N/ABP7 applies to silent (synonymous) variants for which splicing prediction algorithms predict no impact. NM_006758.2:c.132+18del is an intronic deletion, not a synonymous coding variant. Details ▾Hide ▴
Evidence considered
- Intronic variant
- not a synonymous coding change
PS5 N/APS5 is not a standard criterion in the ACMG/AMP 2015 classification framework (Richards et al., PMID:25741868). This variant is assessed under generic ACMG/AMP 2015 rules. Details ▾Hide ▴
Evidence considered
- Not part of standard ACMG/AMP 2015 criteria set
Identifiers
- Gene
- U2AF1
- Transcript
- NM_006758.2
- Coding (HGVS c.)
- NM_006758.2:c.132+18del
- Protein (HGVS p.)
- NP_006749.1:p.?
- GRCh38
- chr21:43104296 GA>G
- GRCh37
- chr21:44524406 GA>G
Gene diagram
Every interpreted variant in U2AF1, mapped onto the exon structure of NM_006758.2. Select a row to find it on the plot.
U2AF1NM_006758.2
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 U2AF1
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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
0 / 6,520 alleles
AF 0 · 0 homozygotes
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0 · 0 / 6,520 alleles · 0 hom
No alternate alleles recorded in the displayed ancestry groups.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0; MAF= 0.00000%, 0/6520 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/370 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingSpliceAI predicts no splice impact for NM_006758.2:c.132+18del (max delta score = 0.00). For an intronic variant, the relevant computational evidence is splice prediction, and the sole applicable in silico tool indicates no effect. Other in silico tools (REVEL, BayesDel) are not applicable to non-SNV variants. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00 — no predicted donor gain
- donor loss
- acceptor gain
- or acceptor loss
- Pangolin scores: splice gain = 0.01
- splice loss = -0.05 (both near zero)
Sources
PP3 No computational evidence supports a deleterious effect. SpliceAI predicts no splice impact (max delta score = 0.00). REVEL and BayesDel are not applicable to non-SNV variants. No in silico tools predict pathogenicity for this intronic deletion. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00 — no splice alteration predicted
- REVEL not applicable (not SNV)
- BayesDel not applicable (not SNV)
Sources
BP7 N/ABP7 applies to silent (synonymous) variants for which splicing prediction algorithms predict no impact. NM_006758.2:c.132+18del is an intronic deletion, not a synonymous coding variant. Details ▾Hide ▴
Evidence considered
- Intronic variant
- not a synonymous coding change
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
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
0 / 6,520 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
Captured ClinVar source record
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/?term=NM_006758.2%3Ac.132%2B18del
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/21-44524406-GA-G?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr21-43104296-GA-G?dataset=g…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/21-43104296-GA-G
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_006758.2%3Ac.132%…
- OncoKB ↗www.oncokb.org/gene/U2AF1/?
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=U2AF1+c.132+18del
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= 0; MAF= 0.00000%, 0/6520 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/370 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant is absent from ClinVar.
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Somatic
This variant has not previously been reported in somatic cancers (COSMIC).