rs5405
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000340.2(SLC2A2):c.661C>T(p.Leu221=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000751 in 1,612,620 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0035 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00047 ( 10 hom. )
Consequence
SLC2A2
NM_000340.2 synonymous
NM_000340.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.23
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 3-171006057-G-A is Benign according to our data. Variant chr3-171006057-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.23 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00349 (531/152160) while in subpopulation AFR AF= 0.0121 (503/41556). AF 95% confidence interval is 0.0112. There are 5 homozygotes in gnomad4. There are 248 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC2A2 | NM_000340.2 | c.661C>T | p.Leu221= | synonymous_variant | 6/11 | ENST00000314251.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC2A2 | ENST00000314251.8 | c.661C>T | p.Leu221= | synonymous_variant | 6/11 | 1 | NM_000340.2 | P1 | |
ENST00000655926.1 | n.291+11032G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00347 AC: 528AN: 152042Hom.: 5 Cov.: 32
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GnomAD3 exomes AF: 0.000979 AC: 245AN: 250198Hom.: 2 AF XY: 0.000740 AC XY: 100AN XY: 135212
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GnomAD4 exome AF: 0.000466 AC: 680AN: 1460460Hom.: 10 Cov.: 31 AF XY: 0.000392 AC XY: 285AN XY: 726562
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GnomAD4 genome AF: 0.00349 AC: 531AN: 152160Hom.: 5 Cov.: 32 AF XY: 0.00333 AC XY: 248AN XY: 74406
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 31, 2017 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 15, 2016 | - - |
Fanconi-Bickel syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2022 | SLC2A2: BP4, BP7, BS1, BS2 - |
SLC2A2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 20, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at