rs5406

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000340.2(SLC2A2):​c.776-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,605,918 control chromosomes in the GnomAD database, including 19,290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4452 hom., cov: 32)
Exomes 𝑓: 0.13 ( 14838 hom. )

Consequence

SLC2A2
NM_000340.2 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.04
Variant links:
Genes affected
SLC2A2 (HGNC:11006): (solute carrier family 2 member 2) This gene encodes an integral plasma membrane glycoprotein of the liver, islet beta cells, intestine, and kidney epithelium. The encoded protein mediates facilitated bidirectional glucose transport. Because of its low affinity for glucose, it has been suggested as a glucose sensor. Mutations in this gene are associated with susceptibility to diseases, including Fanconi-Bickel syndrome and noninsulin-dependent diabetes mellitus (NIDDM). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
Variant 3-171005487-G-A is Benign according to our data. Variant chr3-171005487-G-A is described in ClinVar as [Benign]. Clinvar id is 255900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-171005487-G-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC2A2NM_000340.2 linkc.776-15C>T intron_variant Intron 6 of 10 ENST00000314251.8 NP_000331.1 P11168-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC2A2ENST00000314251.8 linkc.776-15C>T intron_variant Intron 6 of 10 1 NM_000340.2 ENSP00000323568.3 P11168-1

Frequencies

GnomAD3 genomes
AF:
0.208
AC:
31505
AN:
151808
Hom.:
4442
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.406
Gnomad AMI
AF:
0.0758
Gnomad AMR
AF:
0.171
Gnomad ASJ
AF:
0.143
Gnomad EAS
AF:
0.00947
Gnomad SAS
AF:
0.150
Gnomad FIN
AF:
0.129
Gnomad MID
AF:
0.142
Gnomad NFE
AF:
0.132
Gnomad OTH
AF:
0.187
GnomAD3 exomes
AF:
0.142
AC:
35469
AN:
249130
Hom.:
3350
AF XY:
0.141
AC XY:
19045
AN XY:
134720
show subpopulations
Gnomad AFR exome
AF:
0.405
Gnomad AMR exome
AF:
0.115
Gnomad ASJ exome
AF:
0.138
Gnomad EAS exome
AF:
0.00556
Gnomad SAS exome
AF:
0.155
Gnomad FIN exome
AF:
0.131
Gnomad NFE exome
AF:
0.134
Gnomad OTH exome
AF:
0.144
GnomAD4 exome
AF:
0.133
AC:
192893
AN:
1453992
Hom.:
14838
Cov.:
30
AF XY:
0.133
AC XY:
96359
AN XY:
723812
show subpopulations
Gnomad4 AFR exome
AF:
0.414
Gnomad4 AMR exome
AF:
0.121
Gnomad4 ASJ exome
AF:
0.139
Gnomad4 EAS exome
AF:
0.0143
Gnomad4 SAS exome
AF:
0.153
Gnomad4 FIN exome
AF:
0.133
Gnomad4 NFE exome
AF:
0.127
Gnomad4 OTH exome
AF:
0.142
GnomAD4 genome
AF:
0.208
AC:
31544
AN:
151926
Hom.:
4452
Cov.:
32
AF XY:
0.206
AC XY:
15286
AN XY:
74264
show subpopulations
Gnomad4 AFR
AF:
0.406
Gnomad4 AMR
AF:
0.171
Gnomad4 ASJ
AF:
0.143
Gnomad4 EAS
AF:
0.00950
Gnomad4 SAS
AF:
0.150
Gnomad4 FIN
AF:
0.129
Gnomad4 NFE
AF:
0.132
Gnomad4 OTH
AF:
0.189
Alfa
AF:
0.121
Hom.:
435
Bravo
AF:
0.217
Asia WGS
AF:
0.108
AC:
382
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Dec 04, 2015
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Fanconi-Bickel syndrome Benign:2
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Oct 22, 2015
Mayo Clinic Laboratories, Mayo Clinic
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Type 2 diabetes mellitus Benign:1
-
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: research

SLC2A2-rs5406 plays a role in occurence of T2DM. Its associated with neonatal diabetes, glycogen accumulation in liver leading to hepatomegaly. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
CADD
Benign
7.7
DANN
Benign
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs5406; hg19: chr3-170723276; API