chr2-109019449-A-G

Variant names:

• chr2-109019449-A-G
• rs17034806
• XM_047445367.1:c.8370+246403A>G

Variant summary

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

The XM_047445367.1(RANBP2):​c.8370+246403A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,142 control chromosomes in the GnomAD database, including 2,375 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 0.14 (2375 hom., cov: 32)
• Consequence: RANBP2 XM_047445367.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RANBP2	XM_047445367.1	c.8370+246403A>G		intron_variant	Intron 24 of 24		XP_047301323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21915 AN: 152024 Hom.: 2370 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0730

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0440

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0758

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.144 AC: 21956 AN: 152142 Hom.: 2375 Cov.: 32 AF XY: 0.141 AC XY: 10466 AN XY: 74380

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.0730

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.0997

Gnomad4 FIN AF: 0.0440

Gnomad4 NFE AF: 0.0757

Gnomad4 OTH AF: 0.142

Alfa AF: 0.0893 Hom.: 1431

Bravo AF: 0.160

Asia WGS AF: 0.195 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17034806; hg19: chr2-109635905;