Genetic Variant SLC2A2:c.*8delA (chr3-170997894-GT-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_000340.2(SLC2A2):c.*8delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000466 in 1,425,214 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000074 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 0 hom. )

Consequence

SLC2A2
NM_000340.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.929

Publications

0 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: Likely_benign. The variant received -1 ACMG points.

BP6

Variant 3-170997894-GT-G is Benign according to our data. Variant chr3-170997894-GT-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 255893.

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.*8delA	3_prime_UTR	Exon 11 of 11	NP_000331.1	P11168-1
SLC2A2	NM_001278658.2		c.*8delA	3_prime_UTR	Exon 10 of 10	NP_001265587.1	P11168-2
SLC2A2	NM_001278659.2		c.*8delA	3_prime_UTR	Exon 10 of 10	NP_001265588.1	Q6PAU8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC2A2	ENST00000314251.8	TSL:1 MANE Select	c.*8delA	3_prime_UTR	Exon 11 of 11	ENSP00000323568.3	P11168-1
SLC2A2	ENST00000497642.5	TSL:1	n.*1050delA	non_coding_transcript_exon	Exon 10 of 10	ENSP00000418456.1	A0A0C4DH64
SLC2A2	ENST00000497642.5	TSL:1	n.*1050delA	3_prime_UTR	Exon 10 of 10	ENSP00000418456.1	A0A0C4DH64

Frequencies

GnomAD3 genomes

AF:

0.0000743

AC:

AN:

147998

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000124

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000101

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000300

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00168

AC:

280

AN:

167030

AF XY:

0.00170

show subpopulations

Gnomad AFR exome

AF:

0.00136

Gnomad AMR exome

AF:

0.00143

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00163

Gnomad FIN exome

AF:

0.000126

Gnomad NFE exome

AF:

0.00157

Gnomad OTH exome

AF:

0.000763

GnomAD4 exome

AF:

0.000511

AC:

653

AN:

1277124

Hom.:

Cov.:

AF XY:

0.000500

AC XY:

318

AN XY:

636016

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000685

AC:

AN:

29216

American (AMR)

AF:

0.000810

AC:

AN:

39514

Ashkenazi Jewish (ASJ)

AF:

0.000395

AC:

AN:

22786

East Asian (EAS)

AF:

0.0000284

AC:

AN:

35222

South Asian (SAS)

AF:

0.00112

AC:

AN:

74910

European-Finnish (FIN)

AF:

0.000254

AC:

AN:

47326

Middle Eastern (MID)

AF:

0.000766

AC:

AN:

5220

European-Non Finnish (NFE)

AF:

0.000479

AC:

465

AN:

970122

Other (OTH)

AF:

0.000492

AC:

AN:

52808

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.264

Heterozygous variant carriers

197

295

394

492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000743

AC:

AN:

148090

Hom.:

Cov.:

AF XY:

0.0000831

AC XY:

AN XY:

72188

show subpopulations

African (AFR)

AF:

0.000124

AC:

AN:

40338

American (AMR)

AF:

0.000202

AC:

AN:

14818

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3412

East Asian (EAS)

AF:

0.00

AC:

AN:

5090

South Asian (SAS)

AF:

0.00

AC:

AN:

4644

European-Finnish (FIN)

AF:

0.000101

AC:

AN:

9882

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000300

AC:

AN:

66676

Other (OTH)

AF:

0.00

AC:

AN:

2038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

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:

0.00270

Hom.:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Fanconi-Bickel syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.93

Mutation Taster

=100/0

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over