NM_000340.2:c.776-15C>T

Variant names:

• chr3-171005487-G-A
• rs5406
• NM_000340.2:c.776-15C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000340.2(SLC2A2):​c.776-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,605,918 control chromosomes in the GnomAD database, including 19,290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4452 hom., cov: 32)
  • Exomes 𝑓: 0.13 (14838 hom.)
• Consequence: SLC2A2 NM_000340.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.04
• Publications: 17 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 3-171005487-G-A is Benign according to our data. Variant chr3-171005487-G-A is described in ClinVar as Benign. ClinVar VariationId is 255900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A2	NM_000340.2	c.776-15C>T		intron_variant	Intron 6 of 10	ENST00000314251.8	NP_000331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A2	ENST00000314251.8	c.776-15C>T		intron_variant	Intron 6 of 10	1	NM_000340.2	ENSP00000323568.3

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31505 AN: 151808 Hom.: 4442 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.00947

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.187

GnomAD2 exomes AF: 0.142 AC: 35469 AN: 249130 AF XY: 0.141

Gnomad AFR exome AF: 0.405

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.138

Gnomad EAS exome AF: 0.00556

Gnomad FIN exome AF: 0.131

Gnomad NFE exome AF: 0.134

Gnomad OTH exome AF: 0.144

GnomAD4 exome AF: 0.133 AC: 192893 AN: 1453992 Hom.: 14838 Cov.: 30 AF XY: 0.133 AC XY: 96359 AN XY: 723812

African (AFR) AF: 0.414 AC: 13756 AN: 33232

American (AMR) AF: 0.121 AC: 5383 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 3629 AN: 26022

East Asian (EAS) AF: 0.0143 AC: 567 AN: 39646

South Asian (SAS) AF: 0.153 AC: 13138 AN: 86074

European-Finnish (FIN) AF: 0.133 AC: 6983 AN: 52448

Middle Eastern (MID) AF: 0.165 AC: 940 AN: 5694

European-Non Finnish (NFE) AF: 0.127 AC: 139951 AN: 1106266

Other (OTH) AF: 0.142 AC: 8546 AN: 60062

GnomAD4 genome AF: 0.208 AC: 31544 AN: 151926 Hom.: 4452 Cov.: 32 AF XY: 0.206 AC XY: 15286 AN XY: 74264

African (AFR) AF: 0.406 AC: 16825 AN: 41422

American (AMR) AF: 0.171 AC: 2610 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 496 AN: 3468

East Asian (EAS) AF: 0.00950 AC: 49 AN: 5160

South Asian (SAS) AF: 0.150 AC: 724 AN: 4818

European-Finnish (FIN) AF: 0.129 AC: 1364 AN: 10590

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8967 AN: 67900

Other (OTH) AF: 0.189 AC: 399 AN: 2114

Alfa AF: 0.121 Hom.: 435

Bravo AF: 0.217

Asia WGS AF: 0.108 AC: 382 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Dec 04, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fanconi-Bickel syndrome Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Oct 22, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Type 2 diabetes mellitus Benign:1

-

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

SLC2A2-rs5406 plays a role in occurence of T2DM. Its associated with neonatal diabetes, glycogen accumulation in liver leading to hepatomegaly. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.7
DANN	Benign	0.62
PhyloP100		1.0
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: rs5406; hg19: chr3-170723276;