chr2-109019449-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

RANBP2 Gene-Disease associations (from GenCC):

• familial acute necrotizing encephalopathy

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

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

African (AFR) AF: 0.299 AC: 12386 AN: 41462

American (AMR) AF: 0.116 AC: 1781 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0730 AC: 253 AN: 3466

East Asian (EAS) AF: 0.199 AC: 1028 AN: 5160

South Asian (SAS) AF: 0.0997 AC: 480 AN: 4816

European-Finnish (FIN) AF: 0.0440 AC: 467 AN: 10620

Middle Eastern (MID) AF: 0.0925 AC: 27 AN: 292

European-Non Finnish (NFE) AF: 0.0757 AC: 5149 AN: 68014

Other (OTH) AF: 0.142 AC: 301 AN: 2114

Alfa AF: 0.101 Hom.: 4290

Bravo AF: 0.160

Asia WGS AF: 0.195 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.48
PhyloP100		-0.31

Splicing

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

Other links and lift over

dbSNP: rs17034806; hg19: chr2-109635905;