rs11920090

Variant names:

• chr3-170999732-T-A
• rs11920090
• NM_000340.2:c.1069-566A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000340.2(SLC2A2):​c.1069-566A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,022 control chromosomes in the GnomAD database, including 3,696 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3696 hom., cov: 32)
• Consequence: SLC2A2 NM_000340.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133
• Publications: 100 publications found

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

ENSG00000286856 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A2	NM_000340.2	c.1069-566A>T		intron_variant	Intron 8 of 10	ENST00000314251.8	NP_000331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A2	ENST00000314251.8	c.1069-566A>T		intron_variant	Intron 8 of 10	1	NM_000340.2	ENSP00000323568.3

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29488 AN: 151904 Hom.: 3689 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.00928

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.181

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.194 AC: 29526 AN: 152022 Hom.: 3696 Cov.: 32 AF XY: 0.193 AC XY: 14359 AN XY: 74338

African (AFR) AF: 0.359 AC: 14864 AN: 41438

American (AMR) AF: 0.167 AC: 2545 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 516 AN: 3468

East Asian (EAS) AF: 0.00931 AC: 48 AN: 5158

South Asian (SAS) AF: 0.150 AC: 725 AN: 4818

European-Finnish (FIN) AF: 0.129 AC: 1367 AN: 10614

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.132 AC: 8965 AN: 67950

Other (OTH) AF: 0.183 AC: 386 AN: 2112

Alfa AF: 0.136 Hom.: 906

Bravo AF: 0.202

Asia WGS AF: 0.105 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.9
DANN	Benign	0.83
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11920090; hg19: chr3-170717521;