NM_000340.2:c.*8dupA

Variant names:

• chr3-170997894-G-GT
• rs573575421
• NM_000340.2:c.*8dupA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000340.2(SLC2A2):​c.*8dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,337,056 control chromosomes in the GnomAD database, including 5 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0041 (2 hom., cov: 32)
  • Exomes 𝑓: 0.013 (3 hom.)
• Consequence: SLC2A2 NM_000340.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00413 (611/148074) while in subpopulation SAS AF = 0.00667 (31/4646). AF 95% confidence interval is 0.00483. There are 2 homozygotes in GnomAd4. There are 283 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 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.*8dupA		3_prime_UTR	Exon 11 of 11	NP_000331.1	P11168-1
	SLC2A2	NM_001278658.2		c.*8dupA		3_prime_UTR	Exon 10 of 10	NP_001265587.1	P11168-2
	SLC2A2	NM_001278659.2		c.*8dupA		3_prime_UTR	Exon 10 of 10	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.*8dupA		3_prime_UTR	Exon 11 of 11	ENSP00000323568.3	P11168-1
	SLC2A2	ENST00000497642.5	TSL:1	n.*1050dupA		non_coding_transcript_exon	Exon 10 of 10	ENSP00000418456.1	A0A0C4DH64
	SLC2A2	ENST00000497642.5	TSL:1	n.*1050dupA		3_prime_UTR	Exon 10 of 10	ENSP00000418456.1	A0A0C4DH64

Frequencies

GnomAD3 genomes AF: 0.00412 AC: 609 AN: 147984 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00462

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00351

Gnomad ASJ AF: 0.00322

Gnomad EAS AF: 0.000588

Gnomad SAS AF: 0.00645

Gnomad FIN AF: 0.00101

Gnomad MID AF: 0.0162

Gnomad NFE AF: 0.00451

Gnomad OTH AF: 0.00544

GnomAD2 exomes AF: 0.00935 AC: 1561 AN: 167030 AF XY: 0.00985

Gnomad AFR exome AF: 0.00904

Gnomad AMR exome AF: 0.0120

Gnomad ASJ exome AF: 0.00677

Gnomad EAS exome AF: 0.00350

Gnomad FIN exome AF: 0.00259

Gnomad NFE exome AF: 0.00981

Gnomad OTH exome AF: 0.00941

GnomAD4 exome AF: 0.0126 AC: 15039 AN: 1188982 Hom.: 3 Cov.: 30 AF XY: 0.0122 AC XY: 7240 AN XY: 591782

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

African (AFR) AF: 0.0125 AC: 339 AN: 27096

American (AMR) AF: 0.00884 AC: 328 AN: 37100

Ashkenazi Jewish (ASJ) AF: 0.00743 AC: 156 AN: 21002

East Asian (EAS) AF: 0.00245 AC: 80 AN: 32712

South Asian (SAS) AF: 0.0132 AC: 904 AN: 68660

European-Finnish (FIN) AF: 0.00263 AC: 117 AN: 44566

Middle Eastern (MID) AF: 0.0172 AC: 86 AN: 4990

European-Non Finnish (NFE) AF: 0.0138 AC: 12449 AN: 903692

Other (OTH) AF: 0.0118 AC: 580 AN: 49164

⚠️ 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: 0.00413 AC: 611 AN: 148074 Hom.: 2 Cov.: 32 AF XY: 0.00392 AC XY: 283 AN XY: 72176

African (AFR) AF: 0.00461 AC: 186 AN: 40342

American (AMR) AF: 0.00351 AC: 52 AN: 14814

Ashkenazi Jewish (ASJ) AF: 0.00322 AC: 11 AN: 3412

East Asian (EAS) AF: 0.000589 AC: 3 AN: 5090

South Asian (SAS) AF: 0.00667 AC: 31 AN: 4646

European-Finnish (FIN) AF: 0.00101 AC: 10 AN: 9868

Middle Eastern (MID) AF: 0.0175 AC: 5 AN: 286

European-Non Finnish (NFE) AF: 0.00451 AC: 301 AN: 66668

Other (OTH) AF: 0.00588 AC: 12 AN: 2042

Alfa AF: 0.0249 Hom.: 0

Bravo AF: 0.00404

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism

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: rs573575421; hg19: chr3-170715683; COSMIC: COSV58585938; COSMIC: COSV58585938;