rs5400

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000340.2(SLC2A2):c.329C>T(p.Thr110Ile) variant causes a missense change. The variant allele was found at a frequency of 0.143 in 1,613,530 control chromosomes in the GnomAD database, including 21,251 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 5454 hom., cov: 32)

Exomes 𝑓: 0.13 ( 15797 hom. )

Consequence

SLC2A2
NM_000340.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 7.13

Publications

97 publications found

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]

SLC2A2 Gene-Disease associations (from GenCC):

glycogen storage disease due to GLUT2 deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, G2P
neonatal diabetes mellitus
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
permanent neonatal diabetes mellitus
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
transient neonatal diabetes mellitus
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp

SLC2A2 links:

ENSG00000286856 (HGNC:):

ENSG00000286856 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002820909).

BP6

Variant 3-171014511-G-A is Benign according to our data. Variant chr3-171014511-G-A is described in ClinVar as Benign. ClinVar VariationId is 130349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A2	NM_000340.2 link	c.329C>T	p.Thr110Ile	missense_variant	Exon 3 of 11	ENST00000314251.8	NP_000331.1	P11168-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A2	ENST00000314251.8 link	c.329C>T	p.Thr110Ile	missense_variant	Exon 3 of 11	1	NM_000340.2	ENSP00000323568.3		P11168-1

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33796

AN:

151980

Hom.:

5439

Cov.:

show subpopulations

Gnomad AFR

AF:

0.458

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.00925

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.205

GnomAD2 exomes

AF:

0.147

AC:

36820

AN:

251322

AF XY:

0.144

show subpopulations

Gnomad AFR exome

AF:

0.461

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.138

Gnomad EAS exome

AF:

0.00555

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.135

AC:

196835

AN:

1461432

Hom.:

15797

Cov.:

AF XY:

0.135

AC XY:

98005

AN XY:

727040

show subpopulations

African (AFR)

AF:

0.464

AC:

15525

AN:

33462

American (AMR)

AF:

0.124

AC:

5537

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

3649

AN:

26134

East Asian (EAS)

AF:

0.0143

AC:

567

AN:

39696

South Asian (SAS)

AF:

0.153

AC:

13205

AN:

86246

European-Finnish (FIN)

AF:

0.133

AC:

7115

AN:

53418

Middle Eastern (MID)

AF:

0.166

AC:

960

AN:

5768

European-Non Finnish (NFE)

AF:

0.127

AC:

141437

AN:

1111604

Other (OTH)

AF:

0.146

AC:

8840

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

8799

17598

26398

35197

43996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5186

10372

15558

20744

25930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.223

AC:

33852

AN:

152098

Hom.:

5454

Cov.:

AF XY:

0.220

AC XY:

16398

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.458

AC:

18982

AN:

41450

American (AMR)

AF:

0.177

AC:

2711

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

495

AN:

3470

East Asian (EAS)

AF:

0.00927

AC:

AN:

5176

South Asian (SAS)

AF:

0.150

AC:

725

AN:

4826

European-Finnish (FIN)

AF:

0.129

AC:

1363

AN:

10594

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.132

AC:

8984

AN:

67986

Other (OTH)

AF:

0.206

AC:

434

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1202

2405

3607

4810

6012

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.162

Hom.:

10738

Bravo

AF:

0.234

TwinsUK

AF:

0.129

AC:

477

ALSPAC

AF:

0.127

AC:

489

ESP6500AA

AF:

0.447

AC:

1970

ESP6500EA

AF:

0.133

AC:

1147

ExAC

AF:

0.154

AC:

18691

Asia WGS

AF:

0.110

AC:

387

AN:

3478

EpiCase

AF:

0.142

EpiControl

AF:

0.142

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Dec 14, 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:3

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 06, 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. -

not provided

Benign:2

Oct 22, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.041

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.16

DEOGEN2

Benign

0.25

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.7

PhyloP100

7.1

PrimateAI

Benign

0.48

PROVEAN

Benign

3.4

REVEL

Benign

0.17

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.023

MPC

0.15

ClinPred

0.018

GERP RS

6.1

Varity_R

0.044

gMVP

0.22

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over