rs5406

chr3-171005487-G-Achr3-171005487-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000340.2(SLC2A2):c.776-15C>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.04

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id is 255900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-171005487-G-A is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
SLC2A2	NM_000340.2	c.776-15C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000314251.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A2	ENST00000314251.8	c.776-15C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000340.2	P1
	ENST00000655926.1	n.291+10462G>A		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.142 AC: 35469 AN: 249130 Hom.: 3350 AF XY: 0.141 AC XY: 19045 AN XY: 134720

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 SAS exome AF: 0.155

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

Gnomad4 AFR exome AF: 0.414

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.0143

Gnomad4 SAS exome AF: 0.153

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.142

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

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.00950

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.189

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:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 04, 2015	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. -

Fanconi-Bickel syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -

Type 2 diabetes mellitus Benign:1

Benign, criteria provided, single submitter

research

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

-

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

not provided Benign:1

Benign, no assertion criteria provided

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Oct 22, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	7.7
Dann	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs5406; hg19: chr3-170723276;