rs2903696

Positions:

• chr2-109632044-C-T

Variant summary

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

The XM_047445367.1(RANBP2):​c.8371-209360C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0467 in 152,092 control chromosomes in the GnomAD database, including 628 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 0.047 (628 hom., cov: 32)
• Consequence: RANBP2 XM_047445367.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RANBP2	XM_047445367.1	c.8371-209360C>T		intron_variant			XP_047301323.1
		n.109632044C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0466 AC: 7080 AN: 151974 Hom.: 618 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.0517

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.0869

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0200

Gnomad OTH AF: 0.0603

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

GnomAD4 genome AF: 0.0467 AC: 7102 AN: 152092 Hom.: 628 Cov.: 32 AF XY: 0.0513 AC XY: 3811 AN XY: 74346

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.0517

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.0866

Gnomad4 FIN AF: 0.0202

Gnomad4 NFE AF: 0.0200

Gnomad4 OTH AF: 0.0592

Alfa AF: 0.0300 Hom.: 37

Bravo AF: 0.0636

Asia WGS AF: 0.141 AC: 490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2903696; hg19: chr2-110389621;