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.1 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.2 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.3 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).4 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.
SLC2A2
Final classification
VUS
SLC2A2 c.115_117del · p.Ile39del
SLC2A2
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.
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.
Classification rationale
PM2PM4PP5
VUS
SLC2A2 c.115_117del
PM2 + PM4 + PP5
→
VUS
Gene diagram
· NM_000340.2 · variants mapped to exon structure
SLC2A2
NM_000340.2
Fetching transcript structure from UCSC…
Applied criteria · 3 met · select any tile
Met
Not met
Not assessed
N/A
Strength
very strong
supporting
Pathogenic evidence
PVS
PS
PM
PP
Benign evidence
BA
BS
BP
—
—
—
Rationale
Select a criterion.
Sources
Evidence used
Gaps remaining
Rule
—
Research & evidence
Population frequency
gnomAD v4.1
gnomAD v2.1
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.
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.
🇨🇦 CA
This variant is present in gnomAD-Canada v1.0 (AF= 0.00043426338074041906, 8/18422 alleles, homozygotes = 0).
Allele frequency by ancestry
three datasets · side by side
gnomAD v4.1
0.0014%
· 22 / 1,612,532
0 hom · FAF 0.00088%
0 hom · FAF 0.00088%
Remaining individuals 2 / 62,432 |
0.0032% |
Admixed American 1 / 60,004 |
0.0017% |
European (Finnish) 1 / 64,026 |
0.0016% |
European (non-Finnish) 17 / 1,178,644 |
0.0014% |
African/African American 1 / 74,900 |
0.0013% |
+ 5 not observed (Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish)
gnomAD v2.1
0.0028%
· 8 / 282,066
0 hom · FAF 0.0011%
0 hom · FAF 0.0011%
African/African American 2 / 24,640 |
0.0081% |
European (Finnish) 1 / 25,116 |
0.004% |
European (non-Finnish) 5 / 128,812 |
0.0039% |
+ 5 not observed (Admixed American, Ashkenazi Jewish, East Asian, Remaining individuals, South Asian)
gnomAD Canada 🇨🇦
0.043%
· 8 / 18,422
0 hom · FAF 0.034%
0 hom · FAF 0.034%
European (non-Finnish) 8 / 11,742 |
0.068% |
+ 8 not observed (African/African American, Latino/Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Middle Eastern, Remaining individuals, South Asian)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Functional
No data
No calibrated functional assay or RNA evidence was identified for this variant.
COSMIC
Cancer hotspots
Somatic evidence
Not in COSMIC / hotspots
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Hotspots
This variant does not lie in a statistically significant hotspot.
Sources & reference links
Triaged references · 4 PMIDs not cited in assessment
25741868 ↗
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.
CLINVAR
22962670 ↗
Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline.
CLINVAR
23492873 ↗
Recommendations from the EGAPP Working Group: does genomic profiling to assess type 2 diabetes risk improve health outcomes?
CLINVAR