NM_006267.5:c.975+1915G>A

Variant names:

• chr2-108742596-G-A
• rs2059725
• NM_006267.5:c.975+1915G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.95).
• 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 rank	MANE	Protein	UniProt
RANBP2	NM_006267.5	c.975+1915G>A		intron_variant	Intron 7 of 28	ENST00000283195.11	NP_006258.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RANBP2	ENST00000283195.11	c.975+1915G>A		intron_variant	Intron 7 of 28	1	NM_006267.5	ENSP00000283195.6

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

African (AFR) AF: 0.186 AC: 7692 AN: 41444

American (AMR) AF: 0.699 AC: 10692 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2228 AN: 3466

East Asian (EAS) AF: 0.901 AC: 4625 AN: 5134

South Asian (SAS) AF: 0.576 AC: 2775 AN: 4814

European-Finnish (FIN) AF: 0.638 AC: 6727 AN: 10548

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.680 AC: 46190 AN: 67974

Other (OTH) AF: 0.595 AC: 1256 AN: 2112

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
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2059725; hg19: chr2-109359052;