2-109701928-T-C

Variant names:

• chr2-109701928-T-C
• rs951954
• ENST00000732823.1:n.228+7403T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000732823.1(ENSG00000295804):​n.228+7403T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,244 control chromosomes in the GnomAD database, including 55,595 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 0.80 (55595 hom., cov: 33)
• Consequence: ENSG00000295804 ENST00000732823.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290
• Publications: 9 publications found

Genes affected

ENSG00000295804 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RANBP2	XM_047445367.1	c.8371-139476T>C		intron_variant	Intron 24 of 24		XP_047301323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000295804	ENST00000732823.1	n.228+7403T>C		intron_variant	Intron 3 of 3
ENSG00000295804	ENST00000732824.1	n.241+716T>C		intron_variant	Intron 3 of 3
ENSG00000295804	ENST00000732825.1	n.239+716T>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122508 AN: 152126 Hom.: 55582 Cov.: 33

Gnomad AFR AF: 0.343

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.951

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.995

Gnomad OTH AF: 0.871

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

GnomAD4 genome AF: 0.805 AC: 122556 AN: 152244 Hom.: 55595 Cov.: 33 AF XY: 0.812 AC XY: 60431 AN XY: 74448

African (AFR) AF: 0.343 AC: 14249 AN: 41504

American (AMR) AF: 0.919 AC: 14058 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 3299 AN: 3472

East Asian (EAS) AF: 0.974 AC: 5040 AN: 5174

South Asian (SAS) AF: 0.952 AC: 4587 AN: 4820

European-Finnish (FIN) AF: 1.00 AC: 10621 AN: 10624

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.995 AC: 67665 AN: 68034

Other (OTH) AF: 0.871 AC: 1842 AN: 2114

Alfa AF: 0.937 Hom.: 118431

Bravo AF: 0.779

Asia WGS AF: 0.924 AC: 3213 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	1.3
DANN	Benign	0.49
PhyloP100		-0.29

Splicing

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

Other links and lift over

dbSNP: rs951954; hg19: chr2-110459505;