rs2308203

chr2-108784835-T-TTCTAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_006267.5(RANBP2):c.*938_*939insGTCTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,218 control chromosomes in the GnomAD database, including 13,644 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (13631 hom., cov: 0)
  • Exomes 𝑓: 0.23 (13 hom.)
• Consequence: RANBP2 NM_006267.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RANBP2	NM_006267.5	c.*938_*939insGTCTA		3_prime_UTR_variant	29/29	ENST00000283195.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RANBP2	ENST00000283195.11	c.*938_*939insGTCTA		3_prime_UTR_variant	29/29	1	NM_006267.5	P1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55374 AN: 151692 Hom.: 13582 Cov.: 0

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.0904

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.328

GnomAD4 exome AF: 0.226 AC: 93 AN: 412 Hom.: 13 Cov.: 0 AF XY: 0.230 AC XY: 56 AN XY: 244

Gnomad4 FIN exome AF: 0.225

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.365 AC: 55485 AN: 151806 Hom.: 13631 Cov.: 0 AF XY: 0.360 AC XY: 26678 AN XY: 74198

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.0902

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.335

Alfa AF: 0.325 Hom.: 1139

Bravo AF: 0.380

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2308203; hg19: chr2-109401291;