rs8192675

Variant names:

• chr3-171007094-T-C
• rs8192675
• NM_000340.2:c.612+54A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-171007094-T-C
• chr3-171007094-T-A
• chr3-171007094-T-G

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.612+54A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 954,848 control chromosomes in the GnomAD database, including 53,782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (15482 hom., cov: 31)
  • Exomes 𝑓: 0.30 (38300 hom.)
• Consequence: SLC2A2 NM_000340.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.90
• Publications: 85 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: PanelApp Australia, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• 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=-1.0).
• BP6: Variant 3-171007094-T-C is Benign according to our data. Variant chr3-171007094-T-C is described in ClinVar as Benign. ClinVar VariationId is 1292088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000340.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A2	NM_000340.2	MANE Select	c.612+54A>G		intron	N/A	NP_000331.1	P11168-1
	SLC2A2	NM_001278658.2		c.255+54A>G		intron	N/A	NP_001265587.1	P11168-2
	SLC2A2	NM_001278659.2		c.93+54A>G		intron	N/A	NP_001265588.1	Q6PAU8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A2	ENST00000314251.8	TSL:1 MANE Select	c.612+54A>G		intron	N/A	ENSP00000323568.3	P11168-1
	SLC2A2	ENST00000497642.5	TSL:1	n.*79+54A>G		intron	N/A	ENSP00000418456.1	A0A0C4DH64
	SLC2A2	ENST00000878399.1		c.609+54A>G		intron	N/A	ENSP00000548458.1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62026 AN: 151588 Hom.: 15451 Cov.: 31

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.299 AC: 240233 AN: 803142 Hom.: 38300 AF XY: 0.296 AC XY: 125535 AN XY: 424134

African (AFR) AF: 0.720 AC: 14719 AN: 20440

American (AMR) AF: 0.295 AC: 12398 AN: 42036

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 6870 AN: 21782

East Asian (EAS) AF: 0.220 AC: 7876 AN: 35804

South Asian (SAS) AF: 0.278 AC: 19829 AN: 71400

European-Finnish (FIN) AF: 0.262 AC: 13731 AN: 52310

Middle Eastern (MID) AF: 0.333 AC: 1505 AN: 4524

European-Non Finnish (NFE) AF: 0.292 AC: 150440 AN: 516080

Other (OTH) AF: 0.332 AC: 12865 AN: 38766

GnomAD4 genome AF: 0.409 AC: 62105 AN: 151706 Hom.: 15482 Cov.: 31 AF XY: 0.404 AC XY: 29963 AN XY: 74120

African (AFR) AF: 0.712 AC: 29434 AN: 41326

American (AMR) AF: 0.351 AC: 5350 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1142 AN: 3464

East Asian (EAS) AF: 0.227 AC: 1164 AN: 5124

South Asian (SAS) AF: 0.274 AC: 1320 AN: 4818

European-Finnish (FIN) AF: 0.245 AC: 2587 AN: 10566

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19978 AN: 67880

Other (OTH) AF: 0.388 AC: 815 AN: 2100

Alfa AF: 0.348 Hom.: 9496

Bravo AF: 0.431

Asia WGS AF: 0.299 AC: 1043 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.47
DANN	Benign	0.19
PhyloP100		-2.9
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: rs8192675; hg19: chr3-170724883; COSMIC: COSV58586138;