Variant rs6762208 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021627.3(SENP2):c.902C>A(p.Thr301Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,568,588 control chromosomes in the GnomAD database, including 102,731 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.39 ( 11937 hom., cov: 32)

Exomes 𝑓: 0.35 ( 90794 hom. )

Consequence

SENP2
NM_021627.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.38

Variant links:

Genes affected

SENP2 (HGNC:23116): (SUMO specific peptidase 2) SUMO1 (UBL1; MIM 601912) is a small ubiquitin-like protein that can be covalently conjugated to other proteins. SENP2 is one of a group of enzymes that process newly synthesized SUMO1 into the conjugatable form and catalyze the deconjugation of SUMO1-containing species.[supplied by OMIM, Apr 2004]

SENP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.6460668E-5).

BP6

Variant 3-185613377-C-A is Benign according to our data. Variant chr3-185613377-C-A is described in ClinVar as [Benign]. Clinvar id is 1281181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SENP2	NM_021627.3 link	c.902C>A	p.Thr301Lys	missense_variant	10/17	ENST00000296257.10	NP_067640.2	Q9HC62-1
SENP2	XM_005247690.4 link	c.902C>A	p.Thr301Lys	missense_variant	10/16		XP_005247747.2
SENP2	XM_005247691.4 link	c.557C>A	p.Thr186Lys	missense_variant	8/15		XP_005247748.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SENP2	ENST00000296257.10 link	c.902C>A	p.Thr301Lys	missense_variant	10/17	1	NM_021627.3	ENSP00000296257.5		Q9HC62-1

Frequencies

GnomAD3 genomes

AF:

0.391

AC:

59355

AN:

151796

Hom.:

11932

Cov.:

show subpopulations

Gnomad AFR

AF:

0.483

Gnomad AMI

AF:

0.297

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.408

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.557

Gnomad FIN

AF:

0.314

Gnomad MID

AF:

0.404

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.349

GnomAD3 exomes

AF:

0.364

AC:

90355

AN:

248050

Hom.:

17392

AF XY:

0.373

AC XY:

49927

AN XY:

134010

show subpopulations

Gnomad AFR exome

AF:

0.487

Gnomad AMR exome

AF:

0.294

Gnomad ASJ exome

AF:

0.404

Gnomad EAS exome

AF:

0.307

Gnomad SAS exome

AF:

0.540

Gnomad FIN exome

AF:

0.306

Gnomad NFE exome

AF:

0.340

Gnomad OTH exome

AF:

0.349

GnomAD4 exome

AF:

0.350

AC:

496203

AN:

1416674

Hom.:

90794

Cov.:

AF XY:

0.356

AC XY:

251793

AN XY:

706454

show subpopulations

Gnomad4 AFR exome

AF:

0.487

Gnomad4 AMR exome

AF:

0.305

Gnomad4 ASJ exome

AF:

0.412

Gnomad4 EAS exome

AF:

0.342

Gnomad4 SAS exome

AF:

0.535

Gnomad4 FIN exome

AF:

0.305

Gnomad4 NFE exome

AF:

0.334

Gnomad4 OTH exome

AF:

0.355

GnomAD4 genome

AF:

0.391

AC:

59405

AN:

151914

Hom.:

11937

Cov.:

AF XY:

0.394

AC XY:

29253

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.483

Gnomad4 AMR

AF:

0.379

Gnomad4 ASJ

AF:

0.408

Gnomad4 EAS

AF:

0.305

Gnomad4 SAS

AF:

0.557

Gnomad4 FIN

AF:

0.314

Gnomad4 NFE

AF:

0.346

Gnomad4 OTH

AF:

0.348

Alfa

AF:

0.346

Hom.:

19585

Bravo

AF:

0.387

TwinsUK

AF:

0.367

AC:

1359

ALSPAC

AF:

0.343

AC:

1321

ESP6500AA

AF:

0.473

AC:

2082

ESP6500EA

AF:

0.343

AC:

2952

ExAC

AF:

0.373

AC:

45284

Asia WGS

AF:

0.426

AC:

1481

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 13, 2018	This variant is associated with the following publications: (PMID: 29632382, 30012220, 29874175) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.0

DANN

Benign

0.27

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.21

T;T

MetaRNN

Benign

0.000036

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-2.4

N;.

PrimateAI

Benign

0.44

PROVEAN

Benign

1.5

N;N

REVEL

Benign

0.053

Sift

Benign

1.0

T;T

Sift4G

Benign

0.97

T;T

Polyphen

0.0

B;.

Vest4

0.066

MPC

0.50

ClinPred

0.0042

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.023

gMVP

0.45

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over