3-171006940-C-T

Variant names:

• chr3-171006940-C-T
• rs1499821
• NM_000340.2:c.612+208G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000340.2(SLC2A2):​c.612+208G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 151,822 control chromosomes in the GnomAD database, including 1,719 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1719 hom., cov: 32)
• Consequence: SLC2A2 NM_000340.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0190
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-171006940-C-T is Benign according to our data. Variant chr3-171006940-C-T is described in ClinVar as Benign. ClinVar VariationId is 1180919.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A2	NM_000340.2	c.612+208G>A		intron_variant	Intron 5 of 10	ENST00000314251.8	NP_000331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A2	ENST00000314251.8	c.612+208G>A		intron_variant	Intron 5 of 10	1	NM_000340.2	ENSP00000323568.3

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22009 AN: 151704 Hom.: 1721 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.0996

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.155

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.145 AC: 22001 AN: 151822 Hom.: 1719 Cov.: 32 AF XY: 0.142 AC XY: 10569 AN XY: 74194

African (AFR) AF: 0.117 AC: 4841 AN: 41424

American (AMR) AF: 0.157 AC: 2400 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 625 AN: 3460

East Asian (EAS) AF: 0.193 AC: 988 AN: 5130

South Asian (SAS) AF: 0.0997 AC: 479 AN: 4806

European-Finnish (FIN) AF: 0.117 AC: 1232 AN: 10566

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10915 AN: 67882

Other (OTH) AF: 0.152 AC: 320 AN: 2106

Alfa AF: 0.156 Hom.: 5258

Bravo AF: 0.149

Asia WGS AF: 0.150 AC: 518 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.9
DANN	Benign	0.39
PhyloP100		-0.019
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: rs1499821; hg19: chr3-170724729;