chr3-171007166-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000340.2(SLC2A2):c.594G>A(p.Thr198Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,608,914 control chromosomes in the GnomAD database, including 11,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T198T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.15 ( 2402 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8873 hom. )

Consequence

SLC2A2
NM_000340.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.14

Publications

23 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 3-171007166-C-T is Benign according to our data. Variant chr3-171007166-C-T is described in ClinVar as Benign. ClinVar VariationId is 130351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A2	NM_000340.2 link	c.594G>A	p.Thr198Thr	synonymous_variant	Exon 5 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.594G>A	p.Thr198Thr	synonymous_variant	Exon 5 of 11	1	NM_000340.2	ENSP00000323568.3		P11168-1

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23129

AN:

151730

Hom.:

2397

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.00890

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.0930

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.100

Gnomad OTH

AF:

0.144

GnomAD2 exomes

AF:

0.108

AC:

26907

AN:

250208

AF XY:

0.109

show subpopulations

Gnomad AFR exome

AF:

0.289

Gnomad AMR exome

AF:

0.0675

Gnomad ASJ exome

AF:

0.126

Gnomad EAS exome

AF:

0.00589

Gnomad FIN exome

AF:

0.0926

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.114

GnomAD4 exome

AF:

0.103

AC:

149886

AN:

1457066

Hom.:

8873

Cov.:

AF XY:

0.104

AC XY:

75333

AN XY:

725086

show subpopulations

African (AFR)

AF:

0.295

AC:

9809

AN:

33280

American (AMR)

AF:

0.0743

AC:

3310

AN:

44554

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

3350

AN:

26048

East Asian (EAS)

AF:

0.0144

AC:

570

AN:

39646

South Asian (SAS)

AF:

0.131

AC:

11295

AN:

86122

European-Finnish (FIN)

AF:

0.0964

AC:

5145

AN:

53352

Middle Eastern (MID)

AF:

0.139

AC:

802

AN:

5754

European-Non Finnish (NFE)

AF:

0.0983

AC:

108912

AN:

1108134

Other (OTH)

AF:

0.111

AC:

6693

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

6229

12458

18687

24916

31145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4056

8112

12168

16224

20280

<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:

0.152

AC:

23150

AN:

151848

Hom.:

2402

Cov.:

AF XY:

0.151

AC XY:

11190

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.291

AC:

12041

AN:

41378

American (AMR)

AF:

0.118

AC:

1800

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

458

AN:

3464

East Asian (EAS)

AF:

0.00893

AC:

AN:

5154

South Asian (SAS)

AF:

0.132

AC:

633

AN:

4806

European-Finnish (FIN)

AF:

0.0930

AC:

984

AN:

10578

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.100

AC:

6807

AN:

67920

Other (OTH)

AF:

0.142

AC:

299

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

943

1885

2828

3770

4713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<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:

0.117

Hom.:

3034

Bravo

AF:

0.159

Asia WGS

AF:

0.0760

AC:

271

AN:

3478

EpiCase

AF:

0.108

EpiControl

AF:

0.115

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 21, 2016

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

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

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 associated with neonatal diabetes, glycogen accumulation in liver leading to hepatomegaly. rs5404 variant is associated with risk of developing Type II Diabetes Mellitus. However, more studies are required to ascertain the role of rs5404 in neonatal diabetes. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.57

(source)

DANN

Benign

0.45

PhyloP100

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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