rs76362149

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_000340.2(SLC2A2):c.1087G>T(p.Ala363Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,610,670 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 2 hom. )

Consequence

SLC2A2
NM_000340.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: 3.09

Publications

5 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031058013).

BP6

Variant 3-170999148-C-A is Benign according to our data. Variant chr3-170999148-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 199012.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00108 (165/152166) while in subpopulation NFE AF = 0.00159 (108/67990). AF 95% confidence interval is 0.00135. There are 0 homozygotes in GnomAd4. There are 84 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A2	NM_000340.2 link	c.1087G>T	p.Ala363Ser	missense_variant	Exon 9 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.1087G>T	p.Ala363Ser	missense_variant	Exon 9 of 11	1	NM_000340.2	ENSP00000323568.3		P11168-1

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

165

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00443

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00153

AC:

384

AN:

250756

AF XY:

0.00147

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00374

Gnomad NFE exome

AF:

0.00254

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00160

AC:

2327

AN:

1458504

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

1131

AN XY:

725744

show subpopulations

African (AFR)

AF:

0.0000899

AC:

AN:

33370

American (AMR)

AF:

0.0000897

AC:

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26056

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86204

European-Finnish (FIN)

AF:

0.00367

AC:

196

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00186

AC:

2059

AN:

1109192

Other (OTH)

AF:

0.00106

AC:

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

109

217

326

434

543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<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:

0.00108

AC:

165

AN:

152166

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41538

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00443

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00159

AC:

108

AN:

67990

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00150

Hom.:

Bravo

AF:

0.000756

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.00161

AC:

196

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00175

EpiControl

AF:

0.00184

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Fanconi-Bickel syndrome

Uncertain:1Benign:1

Dec 31, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

not provided

Uncertain:1Benign:1

Feb 23, 2015

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 09, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

In silico analysis supports that this missense variant does not alter protein structure/function; Reported as a heterozygous SNP in an individual with myelomeningocele (Ruggiero et al., 2015); This variant is associated with the following publications: (PMID: 30950137, 25776730) -

SLC2A2-related disorder

Benign:1

Sep 11, 2024

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.65

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.90

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.031

MetaSVM

Uncertain

-0.088

MutationAssessor

Benign

1.8

PhyloP100

3.1

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.44

Sift

Uncertain

0.0070

Sift4G

Benign

0.083

Polyphen

0.49

Vest4

0.55

MVP

0.85

MPC

0.43

ClinPred

0.073

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.52

gMVP

0.52

Mutation Taster

=78/22

polymorphism

(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