dbSNP rs5407: SLC2A2:c.1069-9T>C (chr3-170999175-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000340.2(SLC2A2):c.1069-9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,555,948 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 45 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 32 hom. )

Consequence

SLC2A2
NM_000340.2 intron

Scores

Splicing: ADA: 0.0002974

Clinical Significance

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

Conservation

PhyloP100: -0.449

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: PanelApp Australia, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
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 (BayesDel_noAF=-0.86).

BP6

Variant 3-170999175-A-G is Benign according to our data. Variant chr3-170999175-A-G is described in ClinVar as Benign. ClinVar VariationId is 255895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0126 (1925/152220) while in subpopulation AFR AF = 0.0439 (1826/41548). AF 95% confidence interval is 0.0423. There are 45 homozygotes in GnomAd4. There are 930 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 45 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000340.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC2A2	NM_000340.2	MANE Select	c.1069-9T>C	intron	N/A	NP_000331.1	P11168-1
SLC2A2	NM_001278658.2		c.712-9T>C	intron	N/A	NP_001265587.1	P11168-2
SLC2A2	NM_001278659.2		c.550-9T>C	intron	N/A	NP_001265588.1	Q6PAU8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC2A2	ENST00000314251.8	TSL:1 MANE Select	c.1069-9T>C	intron	N/A	ENSP00000323568.3	P11168-1
SLC2A2	ENST00000497642.5	TSL:1	n.*536-9T>C	intron	N/A	ENSP00000418456.1	A0A0C4DH64
SLC2A2	ENST00000878399.1		c.1066-9T>C	intron	N/A	ENSP00000548458.1

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1904

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0436

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00439

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00332

AC:

832

AN:

250448

AF XY:

0.00250

show subpopulations

Gnomad AFR exome

AF:

0.0456

Gnomad AMR exome

AF:

0.00189

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00128

AC:

1791

AN:

1403728

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

750

AN XY:

701920

show subpopulations

African (AFR)

AF:

0.0428

AC:

1384

AN:

32316

American (AMR)

AF:

0.00213

AC:

AN:

44538

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25724

East Asian (EAS)

AF:

0.00

AC:

AN:

39362

South Asian (SAS)

AF:

0.000200

AC:

AN:

85114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00106

AC:

AN:

5672

European-Non Finnish (NFE)

AF:

0.0000784

AC:

AN:

1059270

Other (OTH)

AF:

0.00353

AC:

206

AN:

58370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

171

257

342

428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.0126

AC:

1925

AN:

152220

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

930

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0439

AC:

1826

AN:

41548

American (AMR)

AF:

0.00439

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67990

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

190

285

380

475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00673

Hom.:

Bravo

AF:

0.0142

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Fanconi-Bickel syndrome (2)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.0

(source)

DANN

Benign

0.34

PhyloP100

-0.45

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00030

dbscSNV1_RF

Benign

0.018

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over