NM_000340.2:c.108+1221C>T

Variant names:

• chr3-171017310-G-A
• rs11924032
• NM_000340.2:c.108+1221C>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.108+1221C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 151,918 control chromosomes in the GnomAD database, including 6,677 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 0.29 (6677 hom., cov: 31)
• Consequence: SLC2A2 NM_000340.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• Publications: 22 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A2	NM_000340.2	c.108+1221C>T		intron_variant	Intron 2 of 10	ENST00000314251.8	NP_000331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A2	ENST00000314251.8	c.108+1221C>T		intron_variant	Intron 2 of 10	1	NM_000340.2	ENSP00000323568.3

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43893 AN: 151800 Hom.: 6672 Cov.: 31

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.289 AC: 43911 AN: 151918 Hom.: 6677 Cov.: 31 AF XY: 0.285 AC XY: 21173 AN XY: 74224

African (AFR) AF: 0.382 AC: 15832 AN: 41422

American (AMR) AF: 0.273 AC: 4163 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1101 AN: 3466

East Asian (EAS) AF: 0.203 AC: 1047 AN: 5154

South Asian (SAS) AF: 0.225 AC: 1085 AN: 4816

European-Finnish (FIN) AF: 0.208 AC: 2193 AN: 10542

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17597 AN: 67930

Other (OTH) AF: 0.290 AC: 612 AN: 2112

Alfa AF: 0.266 Hom.: 9000

Bravo AF: 0.298

Asia WGS AF: 0.221 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.52
PhyloP100		0.071
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: rs11924032; hg19: chr3-170735099;