SLC2A2c.115_117delUncertain significance

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Variant interpretation report

SLC2A2 c.115_117del, p.(Ile39del)

NM_000340.2:c.115_117del NP_000331.1:p.(Ile39del) 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 SLC2A2

No gene-level summary was recorded for this case.

Key facts

Evidence used: 3 supporting (pathogenic)
Expert rules: Not recorded
Other laboratories (ClinVar): 2 Likely pathogenic
Pipeline record: 23 Jun 2026

Evidence considered

View criteria

Applied evidence criteria

PM2 (supporting): NM_000340.2:c.115_117del is present at extremely low frequency in gnomAD: v2.1 allele frequency 0.00284% (8/282,066 alleles, 0 homozygotes) and v4.1 allele frequency 0.00136% (22/1,612,532 alleles, 0 homozygotes). Absent from gnomAD-Canada. The allele frequency is well below the 0.1% threshold for PM2.
PM4 (supporting): NM_000340.2:c.115_117del (p.Ile39del) is an in-frame deletion of a single amino acid in exon 3 of SLC2A2, not located in a known repetitive region. In-frame deletions in non-repeat regions meet PM4 at supporting strength per ClinGen SVI guidance.
PP5 (supporting): Two clinical testing laboratories (PreventionGenetics and Fulgent Genetics) have classified NM_000340.2:c.115_117del as Likely pathogenic in ClinVar (Variation ID: 631915). Fulgent Genetics provided ACMG criteria with their submission (SCV005661889). While no expert panel classification exists, two independent clinical laboratories agree on a likely pathogenic classification, meeting PP5 at supporting level.

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: 3 Benign evidence criteria: 0

Pathogenic criteria applied · 3

PM2Supporting

PM2 · supporting

NM_000340.2:c.115_117del is present at extremely low frequency in gnomAD: v2.1 allele frequency 0.00284% (8/282,066 alleles, 0 homozygotes) and v4.1 allele frequency 0.00136% (22/1,612,532 alleles, 0 homozygotes). Absent from gnomAD-Canada. The allele frequency is well below the 0.1% threshold for PM2.

PM4Supporting

PM4 · supporting

NM_000340.2:c.115_117del (p.Ile39del) is an in-frame deletion of a single amino acid in exon 3 of SLC2A2, not located in a known repetitive region. In-frame deletions in non-repeat regions meet PM4 at supporting strength per ClinGen SVI guidance.

PP5Supporting

PP5 · supporting

Two clinical testing laboratories (PreventionGenetics and Fulgent Genetics) have classified NM_000340.2:c.115_117del as Likely pathogenic in ClinVar (Variation ID: 631915). Fulgent Genetics provided ACMG criteria with their submission (SCV005661889). While no expert panel classification exists, two independent clinical laboratories agree on a likely pathogenic classification, meeting PP5 at supporting level.

Benign criteria applied · 0

No benign criterion marked as applied in the recorded assessment.

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, PM4 supporting, PP5 supporting; combination = 3 supporting, 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

22 / 1,612,532 alleles

gnomAD v4.1: 22 / 1,612,532 alleles. Recorded AF 1.36431e-05. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 2.83622e-05; MAF= 0.00284%, 8/282066 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 8.11688e-05; MAF= 0.00812%, 2/24640 alleles, homozygotes = 0); grpmax FAF= 1.124e-05.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.00043426338074041906, 8/18422 alleles, homozygotes = 0).

Applied · PM2 →

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.

No listed criterion applied SpliceAI ↗

ClinVar submissions

2 reported laboratory submissions

2 Likely pathogenic.

Applied · PP5 → 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 ↗

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: 3 met · 4 not met · 14 not assessed · 8 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM3 PM4 PM5 PM6 PP1 PP2 PP3 PP4 PP5 PS5

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP3 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

NM_000340.2:c.115_117del (p.Ile39del) is an in-frame deletion of a single amino acid in exon 3 of SLC2A2, encoding the GLUT2 glucose transporter. Loss-of-function variants in SLC2A2 cause Fanconi-Bickel syndrome (autosomal recessive) and have been implicated in neonatal diabetes.

This variant is present at extremely low frequency in population databases: gnomAD v2.1 allele frequency 0.00284% (8/282,066 alleles, 0 homozygotes) and v4.1 allele frequency 0.00136% (22/1,612,532 alleles, 0 homozygotes). It is absent from gnomAD-Canada.

The variant has been classified as Likely pathogenic in ClinVar (Variation ID: 631915) by two independent clinical testing laboratories, with Fulgent Genetics providing ACMG criteria with their submission.

As an in-frame deletion in a non-repeat region, PM4 (supporting) applies. The variant does not qualify for PVS1, as it is not a null variant (nonsense, frameshift, or canonical splice site).

No variant-specific literature was identified among the four ClinVar-linked PMIDs. PMID:25741868 (ACMG/AMP guidelines) and PMID:22962670 (hypertriglyceridemia guideline) were reviewed in full text; neither mentions NM_000340.2:c.115_117del or SLC2A2. PMID:20301750 (WFS1 Spectrum Disorder) and PMID:23492873 (EGAPP diabetes risk recommendations) are unrelated to this variant.

Met · 3

PM2 SupportingNM_000340.2:c.115_117del is present at extremely low frequency in gnomAD: v2.1 allele frequency 0.00284% (8/282,066 alleles, 0 homozygotes) and v4.1 allele frequency 0.00136% (22/1,612,532 alleles, 0 homozygotes). Absent from gnomAD-Canada. The allele frequency is well below the 0.1% threshold for PM2. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF = 0.0000284 (0.00284%)
8/282
066 alleles
0 homozygotes
gnomAD v4.1 AF = 0.0000136 (0.00136%)
22/1
612
532 alleles
Absent from gnomAD-Canada v1.0

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

PM4 SupportingNM_000340.2:c.115_117del (p.Ile39del) is an in-frame deletion of a single amino acid in exon 3 of SLC2A2, not located in a known repetitive region. In-frame deletions in non-repeat regions meet PM4 at supporting strength per ClinGen SVI guidance. Details ▾Hide ▴

Evidence considered

In-frame deletion of codon 39 (p.Ile39del) in exon 3/11 of SLC2A2
Not in a repetitive region

Sources

pvs1_generic_framework ↗

PP5 SupportingTwo clinical testing laboratories (PreventionGenetics and Fulgent Genetics) have classified NM_000340.2:c.115_117del as Likely pathogenic in ClinVar (Variation ID: 631915). Fulgent Genetics provided ACMG criteria with their submission (SCV005661889). While no expert panel classification exists, two independent clinical laboratories agree on a likely pathogenic classification, meeting PP5 at supporting level. Details ▾Hide ▴

Evidence considered

ClinVar Variation ID 631915: Likely pathogenic
2 clinical laboratory submitters (PreventionGenetics
Fulgent Genetics)
Fulgent Genetics submission (SCV005661889) includes criteria provided

Sources

clinvar ↗

Not met · 4 · evaluated, threshold not reached

BA1 The allele frequency in gnomAD v2.1 (0.00284%) and v4.1 (0.00136%) is far below the BA1 threshold of >1%. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF = 0.00284%
well below 1%
gnomAD v4.1 AF = 0.00136%

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 The allele frequency in gnomAD v2.1 (0.00284%) and v4.1 (0.00136%) is far below the BS1 threshold of >0.3%. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF = 0.00284%
well below 0.3%
gnomAD v4.1 AF = 0.00136%

Sources

gnomad_v2 ↗gnomad_v4 ↗

BP3 BP3 applies to in-frame deletions in repetitive regions without known function. The c.115_117del deletion removes a single isoleucine in exon 3 and is not located in a known repetitive region. Details ▾Hide ▴

Evidence considered

Not in a repetitive region
BP3 does not apply

BP6 BP6 requires a reputable source to classify the variant as benign. This variant is classified as Likely pathogenic in ClinVar by two clinical laboratories; it has not been reported as benign. Details ▾Hide ▴

Evidence considered

ClinVar classification is Likely pathogenic
not benign

Not assessed · 14 · no assessment recorded

PS2 No de novo occurrence data were identified for this variant in ClinVar submissions or the reviewed literature. Details ▾Hide ▴

Still missing

No de novo data available

PS3 One ClinVar submission (SCV004120392, PreventionGenetics) mentions functional studies suggesting impaired glucose uptake, but this submission has no assertion criteria, no validated PMIDs, and the cited study could not be verified. No variant-specific functional study was identified in the reviewed literature. Details ▾Hide ▴

Evidence considered

ClinVar submission SCV004120392 alludes to functional data but lacks verifiable PMID
evidence not confirmable

Still missing

Variant-specific functional assay data not available in reviewed evidence
'Enogieru et al' study referenced by ClinVar submitter but not accessible

PS4 Insufficient case-control or prevalence data to compare affected versus general population frequencies. SLC2A2-related disease (Fanconi-Bickel syndrome) is autosomal recessive, complicating standard PS4 application. Details ▾Hide ▴

Still missing

No case-control data available

PM1 This variant does not lie in a statistically significant mutational hotspot (evidence_brief hotspots: not significant). No curated functional domain or critical-residue data were identified for SLC2A2 residue I39. Details ▾Hide ▴

Evidence considered

Hotspot analysis negative
no domain-level functional annotation for residue I39

Still missing

No SLC2A2 domain/pathogenicity map available for residue-level PM1 assessment

PM6 No de novo occurrence data (with or without confirmed paternity) were identified for this variant. Details ▾Hide ▴

Still missing

No de novo data available

PP1 No cosegregation data were identified for this variant. Details ▾Hide ▴

Still missing

No segregation data available

PP3 In silico prediction tools (REVEL, BayesDel) were not applicable to this non-SNV variant. SpliceAI predicts no splicing impact (max delta = 0.00). HCI prior is not available for SLC2A2. No computational evidence supports a deleterious or benign effect. Details ▾Hide ▴

Evidence considered

SpliceAI max delta = 0.00 (no splice effect)
REVEL/BayesDel/HCI prior unavailable for this variant type or gene

Still missing

No applicable in silico tools for in-frame deletion pathogenicity prediction

Sources

spliceai ↗

PP4 No patient phenotype or clinical data were available for this variant in the reviewed evidence. SLC2A2-related Fanconi-Bickel syndrome has a specific phenotype (hepatomegaly, short stature, hypophosphatemic rickets, glucose/galactose intolerance), but no phenotype-variant correlation data were identified. Details ▾Hide ▴

Still missing

No patient phenotype data available for this variant

BS2 No data on homozygous or hemizygous occurrence in healthy adults were identified. SLC2A2-related disease is autosomal recessive with childhood onset; observation in healthy adults would be informative but is not available. Details ▾Hide ▴

Still missing

No healthy adult observed homozygous data available

BS3 No well-established functional studies showing no deleterious effect were identified for this variant. Details ▾Hide ▴

Still missing

No benign functional data available

BS4 No nonsegregation data were identified for this variant. Details ▾Hide ▴

Still missing

No segregation data available

BP2 No data on observation in trans with a dominant pathogenic variant were identified. Details ▾Hide ▴

Still missing

No trans-configuration data available

BP4 SpliceAI predicts no splicing impact (max delta = 0.00), but REVEL and BayesDel are not applicable to non-SNV variants. Insufficient computational evidence is available to support a benign prediction for an in-frame deletion. Details ▾Hide ▴

Evidence considered

SpliceAI max delta = 0.00 (no splice effect)
no other in silico tools applicable

Still missing

No applicable in silico tools for in-frame deletion impact prediction

Sources

spliceai ↗

BP5 No data on this variant being found in a case with an alternate molecular basis for disease were identified. Details ▾Hide ▴

Still missing

No alternate molecular basis data available

Not applicable · 8· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/ANM_000340.2:c.115_117del is an in-frame 3-bp deletion (p.Ile39del), which does not fall into the generic PVS1 null-variant buckets of nonsense, frameshift, or canonical ±1,2 splice consensus variants. The ClinGen SVI PVS1 framework does not apply to in-frame deletions. Details ▾Hide ▴

Evidence considered

In-frame deletion
not a null variant per ClinGen SVI PVS1 criteria (PMC6185798)

Sources

pvs1_generic_framework ↗

PS1 N/APS1 applies to a different nucleotide change producing the same amino acid change as an established pathogenic variant. This variant is an in-frame deletion (p.Ile39del), not a missense substitution, and no established pathogenic single-nucleotide variant at the same residue was identified. Details ▾Hide ▴

Evidence considered

In-frame deletion is not a missense change
PS1 semantics do not apply

PM3 N/ASkipped per instruction; trivially not applicable. Details ▾Hide ▴

No further detail was recorded.

PM5 N/APM5 applies to a novel missense change at the same amino acid residue as a known pathogenic missense variant. This is an in-frame deletion, not a missense change, and PM5 candidate harvesting found no eligible comparators. Details ▾Hide ▴

Evidence considered

In-frame deletion
PM5 is designed for missense comparator variants
pm5_candidates.json returned no candidates

PP2 N/APP2 applies to missense variants in genes with a low rate of benign missense variation. This is an in-frame deletion, not a missense variant. Details ▾Hide ▴

Evidence considered

In-frame deletion
not a missense variant

BP1 N/ABP1 applies to missense variants in genes where only truncating variants cause disease. This is an in-frame deletion and SLC2A2 has both missense and loss-of-function variants associated with disease (Fanconi-Bickel syndrome, neonatal diabetes). Details ▾Hide ▴

Evidence considered

SLC2A2 disease mechanism includes both missense and LOF variants
BP1 does not apply

BP7 N/ABP7 applies to synonymous variants with no predicted splice impact. This is an in-frame deletion (p.Ile39del), not a synonymous variant. Details ▾Hide ▴

Evidence considered

In-frame deletion
not a synonymous variant

PS5 N/APS5 applies when a different pathogenic variant at the same residue has been established from a reputable source. This is an in-frame deletion, not a missense change, and no known pathogenic missense at residue I39 was identified. Details ▾Hide ▴

Evidence considered

In-frame deletion
PS5 is designed for missense comparator variants

Identifiers

Gene: SLC2A2
Transcript: NM_000340.2
Coding (HGVS c.): NM_000340.2:c.115_117del
Protein (HGVS p.): NP_000331.1:p.(Ile39del)
GRCh38: chr3:171014722 ATAT>A
GRCh37: chr3:170732511 ATAT>A
ClinVar: 631915

Gene diagram

Every interpreted variant in SLC2A2, mapped onto the exon structure of NM_000340.2. Select a row to find it on the plot.

SLC2A2NM_000340.2

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 SLC2A2 — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 22 / 1,612,532 alleles AF 1.36e-05 · 0 homozygotes · FAF 8.79e-06

gnomAD v2.1 8 / 282,066 alleles AF 2.84e-05 · 0 homozygotes · FAF 1.12e-05

gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 1.4e-05 · 22 / 1,612,532 alleles · 0 hom · FAF 8.8e-06

Remaining individuals2 / 62,432	3.2e-05
Admixed American1 / 60,004	1.7e-05
European (Finnish)1 / 64,026	1.6e-05
European (non-Finnish)17 / 1,178,644	1.4e-05
African/African American1 / 74,900	1.3e-05

0 alternate alleles recorded in 5 other groups: Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish.

gnomAD v2.1

AF 2.8e-05 · 8 / 282,066 alleles · 0 hom · FAF 1.1e-05

African/African American2 / 24,640	8.1e-05
European (Finnish)1 / 25,116	4e-05
European (non-Finnish)5 / 128,812	3.9e-05

0 alternate alleles recorded in 5 other groups: Admixed American, Ashkenazi Jewish, East Asian, Remaining individuals, South Asian.

gnomAD-Canada

AF not recorded · ? / ? alleles

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 1.36431e-05; MAF= 0.00136%, 22/1612532 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 3.20349e-05; MAF= 0.00320%, 2/62432 alleles, homozygotes = 0); grpmax FAF= 8.79e-06.

gnomAD v2.1

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.00043426338074041906, 8/18422 alleles, homozygotes = 0).

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

SpliceAI acceptor lossat +461 bp

0.000

SpliceAI acceptor gainat -245 bp

0.000

SpliceAI donor lossat -6 bp

0.000

SpliceAI donor gainat -119 bp

0.000

Other predictors

REVEL: Not available
BayesDel: Not available

How the predictions were used

Evidence considered

SpliceAI max delta = 0.00 (no splice effect)
REVEL/BayesDel/HCI prior unavailable for this variant type or gene

Still missing

No applicable in silico tools for in-frame deletion pathogenicity prediction

Sources

spliceai ↗

Evidence considered

SpliceAI max delta = 0.00 (no splice effect)
no other in silico tools applicable

Still missing

No applicable in silico tools for in-frame deletion impact prediction

Sources

spliceai ↗

BP7 N/ABP7 applies to synonymous variants with no predicted splice impact. This is an in-frame deletion (p.Ile39del), not a synonymous variant. Details ▾Hide ▴

Evidence considered

In-frame deletion
not a synonymous variant

Statement

In silico

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

4 paper records 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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S et al. · 2015

This is the ACMG/AMP standards and guidelines for sequence variant interpretation. It defines the generic classification framework used in this assessment and does not discuss NM_000340.2:c.115_117del or SLC2A2.
Does not name this variant
PMID 25741868 ↗
WFS1 Spectrum Disorder.

Adam MP et al. · 1993

This is a GeneReviews entry on WFS1 Spectrum Disorder (Wolfram syndrome), caused by mutations in the WFS1 gene. It does not discuss NM_000340.2:c.115_117del, SLC2A2, or Fanconi-Bickel syndrome.
Does not name this variant
PMID 20301750 ↗
Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline.

Berglund L et al. · 2012

This is an Endocrine Society clinical practice guideline on evaluation and treatment of hypertriglyceridemia. It does not discuss NM_000340.2:c.115_117del, SLC2A2, GLUT2, or Fanconi-Bickel syndrome.
Does not name this variant
PMID 22962670 ↗
Recommendations from the EGAPP Working Group: does genomic profiling to assess type 2 diabetes risk improve health outcomes?

Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group et al. · 2013

This is an EGAPP Working Group recommendation on genomic profiling for type 2 diabetes risk assessment. It does not discuss NM_000340.2:c.115_117del, SLC2A2, or Fanconi-Bickel syndrome.
Does not name this variant
PMID 23492873 ↗

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

gnomAD v4.1 22 / 1,612,532 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 2 Likely pathogenic Open source ↗

COSMIC Captured COSMIC source record Open source ↗

Cancer hotspots Captured Cancer Hotspots 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

gnomAD v2.1

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.00043426338074041906, 8/18422 alleles, homozygotes = 0).

ClinVar

Error retrieving ClinVar entry.

In silico

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

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.