rs200515712

chr2-108762123-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_006267.5(RANBP2):c.2625A>G(p.Val875=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000263 in 1,596,240 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00027 (4 hom.)
• Consequence: RANBP2 NM_006267.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.213

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 2-108762123-A-G is Benign according to our data. Variant chr2-108762123-A-G is described in ClinVar as [Benign]. Clinvar id is 469443.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.213 with no splicing effect.
• BS2: High AC in GnomAd at 29 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RANBP2	NM_006267.5	c.2625A>G	p.Val875=	synonymous_variant	19/29	ENST00000283195.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RANBP2	ENST00000283195.11	c.2625A>G	p.Val875=	synonymous_variant	19/29	1	NM_006267.5	P1
RANBP2	ENST00000697737.1	c.2602+3575A>G		intron_variant
RANBP2	ENST00000697740.1	c.2524+3575A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 151628 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000727

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00483

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000314 AC: 74 AN: 235626 Hom.: 0 AF XY: 0.000302 AC XY: 39 AN XY: 128948

Gnomad AFR exome AF: 0.0000679

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00390

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000903

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.000271 AC: 391 AN: 1444494 Hom.: 4 Cov.: 31 AF XY: 0.000271 AC XY: 195 AN XY: 718970

Gnomad4 AFR exome AF: 0.0000600

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00942

Gnomad4 SAS exome AF: 0.0000697

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.0000999

GnomAD4 genome AF: 0.000191 AC: 29 AN: 151746 Hom.: 0 Cov.: 27 AF XY: 0.000229 AC XY: 17 AN XY: 74140

Gnomad4 AFR AF: 0.0000725

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00484

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000144

EpiCase AF: 0.0000547

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial acute necrotizing encephalopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 04, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	7.9
Dann	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs200515712; hg19: chr2-109378579;