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GeneBe

rs826580

chr2-108773007-G-Achr2-108773007-G-Cchr2-108773007-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_006267.5(RANBP2):c.8253G>A(p.Glu2751=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 1,613,836 control chromosomes in the GnomAD database, including 803,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.99 ( 74410 hom., cov: 33)
Exomes 𝑓: 1.0 ( 728956 hom. )

Consequence

RANBP2
NM_006267.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.53
Variant links:
Genes affected
RANBP2 (HGNC:9848): (RAN binding protein 2) RAN is a small GTP-binding protein of the RAS superfamily that is associated with the nuclear membrane and is thought to control a variety of cellular functions through its interactions with other proteins. This gene encodes a very large RAN-binding protein that immunolocalizes to the nuclear pore complex. The protein is a giant scaffold and mosaic cyclophilin-related nucleoporin implicated in the Ran-GTPase cycle. The encoded protein directly interacts with the E2 enzyme UBC9 and strongly enhances SUMO1 transfer from UBC9 to the SUMO1 target SP100. These findings place sumoylation at the cytoplasmic filaments of the nuclear pore complex and suggest that, for some substrates, modification and nuclear import are linked events. This gene is partially duplicated in a gene cluster that lies in a hot spot for recombination on chromosome 2q. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-108773007-G-A is Benign according to our data. Variant chr2-108773007-G-A is described in ClinVar as [Benign]. Clinvar id is 1169866.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.53 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RANBP2NM_006267.5 linkuse as main transcriptc.8253G>A p.Glu2751= synonymous_variant 23/29 ENST00000283195.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RANBP2ENST00000283195.11 linkuse as main transcriptc.8253G>A p.Glu2751= synonymous_variant 23/291 NM_006267.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.988
AC:
150424
AN:
152226
Hom.:
74351
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.959
Gnomad AMI
AF:
1.00
Gnomad AMR
AF:
0.996
Gnomad ASJ
AF:
1.00
Gnomad EAS
AF:
1.00
Gnomad SAS
AF:
1.00
Gnomad FIN
AF:
1.00
Gnomad MID
AF:
0.997
Gnomad NFE
AF:
1.00
Gnomad OTH
AF:
0.991
GnomAD3 exomes
AF:
0.997
AC:
250047
AN:
250850
Hom.:
124644
AF XY:
0.998
AC XY:
135277
AN XY:
135570
show subpopulations
Gnomad AFR exome
AF:
0.957
Gnomad AMR exome
AF:
0.998
Gnomad ASJ exome
AF:
1.00
Gnomad EAS exome
AF:
1.00
Gnomad SAS exome
AF:
1.00
Gnomad FIN exome
AF:
1.00
Gnomad NFE exome
AF:
1.00
Gnomad OTH exome
AF:
0.999
GnomAD4 exome
AF:
0.999
AC:
1459656
AN:
1461492
Hom.:
728956
Cov.:
54
AF XY:
0.999
AC XY:
726249
AN XY:
727022
show subpopulations
Gnomad4 AFR exome
AF:
0.958
Gnomad4 AMR exome
AF:
0.998
Gnomad4 ASJ exome
AF:
1.00
Gnomad4 EAS exome
AF:
1.00
Gnomad4 SAS exome
AF:
1.00
Gnomad4 FIN exome
AF:
1.00
Gnomad4 NFE exome
AF:
1.00
Gnomad4 OTH exome
AF:
0.997
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.988
AC:
150542
AN:
152344
Hom.:
74410
Cov.:
33
AF XY:
0.989
AC XY:
73674
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.959
Gnomad4 AMR
AF:
0.996
Gnomad4 ASJ
AF:
1.00
Gnomad4 EAS
AF:
1.00
Gnomad4 SAS
AF:
1.00
Gnomad4 FIN
AF:
1.00
Gnomad4 NFE
AF:
1.00
Gnomad4 OTH
AF:
0.991
Alfa
AF:
0.995
Hom.:
43668
Bravo
AF:
0.986
Asia WGS
AF:
0.998
AC:
3469
AN:
3478
EpiCase
AF:
1.00
EpiControl
AF:
1.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Familial acute necrotizing encephalopathy Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
Cadd
Benign
3.9
Dann
Benign
0.47
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs826580; hg19: chr2-109389463; API