rs746295534

Variant names:

• chr3-171009950-T-TGTGA
• rs746295534
• NM_000340.2:c.496+7_496+8insTCAC

Your query was ambiguous. Multiple possible variants found:

• chr3-171009950-T-TGTGA
• chr3-171009950-T-TGTGTGTGA
• chr3-171009950-T-TGTGTGTGTGA
• chr3-171009950-T-TGTGTGTGTGTGTGTGTGA
• chr3-171009950-T-TGTGTGA
• chr3-171009950-T-TGTGTGTGTGTGTGTGA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_000340.2(SLC2A2):​c.496+7_496+8insTCAC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000642 in 1,541,406 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (2 hom.)
• Consequence: SLC2A2 NM_000340.2 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.189
• Publications: 0 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 -16 ACMG points.

• BP6: Variant 3-171009950-T-TGTGA is Benign according to our data. Variant chr3-171009950-T-TGTGA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 540254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00391 (590/150856) while in subpopulation AFR AF = 0.0131 (535/40912). AF 95% confidence interval is 0.0122. There are 6 homozygotes in GnomAd4. There are 270 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

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.496+7_496+8insTCAC		splice_region intron	N/A	NP_000331.1	P11168-1
	SLC2A2	NM_001278658.2		c.139+7_139+8insTCAC		splice_region intron	N/A	NP_001265587.1	P11168-2
	SLC2A2	NM_001278659.2		c.-23-2688_-23-2687insTCAC		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.496+7_496+8insTCAC		splice_region intron	N/A	ENSP00000323568.3	P11168-1
	SLC2A2	ENST00000497642.5	TSL:1	n.372-2688_372-2687insTCAC		intron	N/A	ENSP00000418456.1	A0A0C4DH64
	SLC2A2	ENST00000878399.1		c.493+10_493+11insTCAC		intron	N/A	ENSP00000548458.1

Frequencies

GnomAD3 genomes AF: 0.00389 AC: 586 AN: 150738 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00232

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000420

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000738

Gnomad OTH AF: 0.00632

GnomAD2 exomes AF: 0.000537 AC: 100 AN: 186318 AF XY: 0.000369

Gnomad AFR exome AF: 0.00929

Gnomad AMR exome AF: 0.000512

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000123

Gnomad OTH exome AF: 0.000625

GnomAD4 exome AF: 0.000287 AC: 399 AN: 1390550 Hom.: 2 Cov.: 37 AF XY: 0.000233 AC XY: 161 AN XY: 690238

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0100 AC: 308 AN: 30704

American (AMR) AF: 0.000451 AC: 18 AN: 39898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24962

East Asian (EAS) AF: 0.00 AC: 0 AN: 38676

South Asian (SAS) AF: 0.0000367 AC: 3 AN: 81656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47060

Middle Eastern (MID) AF: 0.00111 AC: 6 AN: 5412

European-Non Finnish (NFE) AF: 0.0000132 AC: 14 AN: 1064550

Other (OTH) AF: 0.000868 AC: 50 AN: 57632

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00391 AC: 590 AN: 150856 Hom.: 6 Cov.: 32 AF XY: 0.00367 AC XY: 270 AN XY: 73624

African (AFR) AF: 0.0131 AC: 535 AN: 40912

American (AMR) AF: 0.00231 AC: 35 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.000420 AC: 2 AN: 4758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000738 AC: 5 AN: 67714

Other (OTH) AF: 0.00626 AC: 13 AN: 2078

Alfa AF: 0.0000500 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Fanconi-Bickel syndrome (1)
-	-	1	not specified (1)
-	-	1	SLC2A2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs746295534; hg19: chr3-170727739;