rs10513684

Variant names:

• chr3-171006421-C-T
• rs10513684
• NM_000340.2:c.613-316G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000340.2(SLC2A2):​c.613-316G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 152,072 control chromosomes in the GnomAD database, including 175 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 0.047 (175 hom., cov: 32)
• Consequence: SLC2A2 NM_000340.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64
• Publications: 10 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=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0466 (7094/152072) while in subpopulation NFE AF = 0.0492 (3342/67930). AF 95% confidence interval is 0.0478. There are 175 homozygotes in GnomAd4. There are 3531 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 175 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A2	NM_000340.2	c.613-316G>A		intron_variant	Intron 5 of 10	ENST00000314251.8	NP_000331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A2	ENST00000314251.8	c.613-316G>A		intron_variant	Intron 5 of 10	1	NM_000340.2	ENSP00000323568.3

Frequencies

GnomAD3 genomes AF: 0.0467 AC: 7092 AN: 151954 Hom.: 175 Cov.: 32

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0462

Gnomad ASJ AF: 0.0923

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0846

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0492

Gnomad OTH AF: 0.0503

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

GnomAD4 genome AF: 0.0466 AC: 7094 AN: 152072 Hom.: 175 Cov.: 32 AF XY: 0.0475 AC XY: 3531 AN XY: 74336

African (AFR) AF: 0.0379 AC: 1573 AN: 41506

American (AMR) AF: 0.0462 AC: 705 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0923 AC: 320 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.0244 AC: 118 AN: 4832

European-Finnish (FIN) AF: 0.0846 AC: 897 AN: 10598

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0492 AC: 3342 AN: 67930

Other (OTH) AF: 0.0498 AC: 105 AN: 2110

Alfa AF: 0.0471 Hom.: 140

Bravo AF: 0.0435

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.063
DANN	Benign	0.48
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism

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: rs10513684; hg19: chr3-170724210;