rs2059725

Positions:

• chr2-108742596-G-A
• chr2-108742596-G-C
• chr2-108742596-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006267.5(RANBP2):​c.975+1915G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,984 control chromosomes in the GnomAD database, including 26,720 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (26720 hom., cov: 32)
• Consequence: RANBP2 NM_006267.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.541

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RANBP2	NM_006267.5	c.975+1915G>A		intron_variant		ENST00000283195.11	NP_006258.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RANBP2	ENST00000283195.11	c.975+1915G>A		intron_variant		1	NM_006267.5	ENSP00000283195	P1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82970 AN: 151866 Hom.: 26726 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.546 AC: 82967 AN: 151984 Hom.: 26720 Cov.: 32 AF XY: 0.549 AC XY: 40753 AN XY: 74270

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.699

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.901

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.595

Alfa AF: 0.593 Hom.: 3658

Bravo AF: 0.541

Asia WGS AF: 0.613 AC: 2130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.6
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs2059725; hg19: chr2-109359052;