rs10513689

Variant names:

• chr3-171009869-G-A
• rs10513689
• NM_000340.2:c.496+89C>T

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.496+89C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,481,410 control chromosomes in the GnomAD database, including 18,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4521 hom., cov: 31)
  • Exomes 𝑓: 0.13 (13946 hom.)
• Consequence: SLC2A2 NM_000340.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.308
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 3-171009869-G-A is Benign according to our data. Variant chr3-171009869-G-A is described in ClinVar as Benign. ClinVar VariationId is 1264817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A2	NM_000340.2	c.496+89C>T		intron_variant	Intron 4 of 10	ENST00000314251.8	NP_000331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A2	ENST00000314251.8	c.496+89C>T		intron_variant	Intron 4 of 10	1	NM_000340.2	ENSP00000323568.3

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31548 AN: 151148 Hom.: 4510 Cov.: 31

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.00913

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.128 AC: 170078 AN: 1330144 Hom.: 13946 AF XY: 0.128 AC XY: 84464 AN XY: 658284

African (AFR) AF: 0.419 AC: 12442 AN: 29694

American (AMR) AF: 0.123 AC: 4320 AN: 35074

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 3306 AN: 24216

East Asian (EAS) AF: 0.0150 AC: 522 AN: 34742

South Asian (SAS) AF: 0.148 AC: 11468 AN: 77276

European-Finnish (FIN) AF: 0.132 AC: 4714 AN: 35678

Middle Eastern (MID) AF: 0.164 AC: 762 AN: 4634

European-Non Finnish (NFE) AF: 0.121 AC: 124877 AN: 1033556

Other (OTH) AF: 0.139 AC: 7667 AN: 55274

GnomAD4 genome AF: 0.209 AC: 31588 AN: 151266 Hom.: 4521 Cov.: 31 AF XY: 0.207 AC XY: 15301 AN XY: 73862

African (AFR) AF: 0.412 AC: 16926 AN: 41104

American (AMR) AF: 0.172 AC: 2602 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 495 AN: 3464

East Asian (EAS) AF: 0.00915 AC: 47 AN: 5136

South Asian (SAS) AF: 0.149 AC: 714 AN: 4778

European-Finnish (FIN) AF: 0.128 AC: 1345 AN: 10504

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.132 AC: 8957 AN: 67818

Other (OTH) AF: 0.187 AC: 392 AN: 2098

Alfa AF: 0.182 Hom.: 539

Bravo AF: 0.219

Asia WGS AF: 0.107 AC: 378 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

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	-0.98
CADD	Benign	0.63
DANN	Benign	0.28
PhyloP100		0.31
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: rs10513689; hg19: chr3-170727658;