rs5398

Positions:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_000340.2(SLC2A2):c.1437C>T(p.Phe479=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,613,122 control chromosomes in the GnomAD database, including 78,050 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.38 ( 12175 hom., cov: 32)

Exomes 𝑓: 0.30 ( 65875 hom. )

Consequence

SLC2A2
NM_000340.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:8

Conservation

PhyloP100: -0.739

Variant links:

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 3-170998041-G-A is Benign according to our data. Variant chr3-170998041-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 130348.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=6}. Variant chr3-170998041-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.739 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A2	NM_000340.2 linkuse as main transcript	c.1437C>T	p.Phe479=	synonymous_variant	11/11	ENST00000314251.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A2	ENST00000314251.8 linkuse as main transcript	c.1437C>T	p.Phe479=	synonymous_variant	11/11	1	NM_000340.2	P1	P11168-1
SLC2A2	ENST00000497642.5 linkuse as main transcript	c.*904C>T		3_prime_UTR_variant, NMD_transcript_variant	10/10	1
	ENST00000655926.1 linkuse as main transcript	n.291+3016G>A		intron_variant, non_coding_transcript_variant
SLC2A2	ENST00000469787.1 linkuse as main transcript	c.*904C>T		3_prime_UTR_variant, NMD_transcript_variant	10/10	2

Frequencies

GnomAD3 genomes

AF:

0.375

AC:

56935

AN:

151836

Hom.:

12148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.594

Gnomad AMI

AF:

0.243

Gnomad AMR

AF:

0.341

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.244

Gnomad MID

AF:

0.322

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.366

GnomAD3 exomes

AF:

0.307

AC:

76887

AN:

250066

Hom.:

12705

AF XY:

0.304

AC XY:

41164

AN XY:

135376

show subpopulations

Gnomad AFR exome

AF:

0.602

Gnomad AMR exome

AF:

0.285

Gnomad ASJ exome

AF:

0.316

Gnomad EAS exome

AF:

0.235

Gnomad SAS exome

AF:

0.282

Gnomad FIN exome

AF:

0.262

Gnomad NFE exome

AF:

0.299

Gnomad OTH exome

AF:

0.307

GnomAD4 exome

AF:

0.295

AC:

431072

AN:

1461168

Hom.:

65875

Cov.:

AF XY:

0.293

AC XY:

213184

AN XY:

726908

show subpopulations

Gnomad4 AFR exome

AF:

0.605

Gnomad4 AMR exome

AF:

0.291

Gnomad4 ASJ exome

AF:

0.317

Gnomad4 EAS exome

AF:

0.223

Gnomad4 SAS exome

AF:

0.279

Gnomad4 FIN exome

AF:

0.263

Gnomad4 NFE exome

AF:

0.289

Gnomad4 OTH exome

AF:

0.318

GnomAD4 genome

AF:

0.375

AC:

57005

AN:

151954

Hom.:

12175

Cov.:

AF XY:

0.371

AC XY:

27569

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.595

Gnomad4 AMR

AF:

0.340

Gnomad4 ASJ

AF:

0.329

Gnomad4 EAS

AF:

0.231

Gnomad4 SAS

AF:

0.273

Gnomad4 FIN

AF:

0.244

Gnomad4 NFE

AF:

0.292

Gnomad4 OTH

AF:

0.364

Alfa

AF:

0.308

Hom.:

17610

Bravo

AF:

0.392

Asia WGS

AF:

0.290

AC:

1012

AN:

3478

EpiCase

AF:

0.301

EpiControl

AF:

0.298

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:8

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 21, 2016	p.Phe479Phe in exon 11 of SLC2A2: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 63.54% (840/1322) of African chromosomes by the 1000 Genomes Project (Phase 3; dbSNP rs5398). -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 04, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Fanconi-Bickel syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Type 2 diabetes mellitus

Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Associated with neonatal diabetes, glycogen accumulation in liver leading to hepatomegaly. -

not provided

Benign:1

Benign, no assertion criteria provided

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Oct 22, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.0

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over