Genetic Variant SENP2:p.Thr301Lys (chr3-185613377-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

62 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SENP2	NM_021627.3 link	c.902C>A	p.Thr301Lys	missense_variant	Exon 10 of 17	ENST00000296257.10	NP_067640.2	Q9HC62-1
SENP2	XM_005247690.4 link	c.902C>A	p.Thr301Lys	missense_variant	Exon 10 of 16		XP_005247747.2
SENP2	XM_005247691.4 link	c.557C>A	p.Thr186Lys	missense_variant	Exon 8 of 15		XP_005247748.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SENP2	ENST00000296257.10 link	c.902C>A	p.Thr301Lys	missense_variant	Exon 10 of 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

GnomAD2 exomes

AF:

0.364

AC:

90355

AN:

248050

AF XY:

0.373

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 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

African (AFR)

AF:

0.487

AC:

15689

AN:

32194

American (AMR)

AF:

0.305

AC:

13456

AN:

44058

Ashkenazi Jewish (ASJ)

AF:

0.412

AC:

10591

AN:

25688

East Asian (EAS)

AF:

0.342

AC:

13448

AN:

39302

South Asian (SAS)

AF:

0.535

AC:

44644

AN:

83490

European-Finnish (FIN)

AF:

0.305

AC:

16202

AN:

53056

Middle Eastern (MID)

AF:

0.414

AC:

2338

AN:

5654

European-Non Finnish (NFE)

AF:

0.334

AC:

358974

AN:

1074504

Other (OTH)

AF:

0.355

AC:

20861

AN:

58728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

Heterozygous variant carriers

13516

27032

40547

54063

67579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11506

23012

34518

46024

57530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.391

AC:

59405

AN:

151914

Hom.:

11937

Cov.:

AF XY:

0.394

AC XY:

29253

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.483

AC:

19982

AN:

41410

American (AMR)

AF:

0.379

AC:

5780

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.408

AC:

1415

AN:

3470

East Asian (EAS)

AF:

0.305

AC:

1583

AN:

5182

South Asian (SAS)

AF:

0.557

AC:

2677

AN:

4808

European-Finnish (FIN)

AF:

0.314

AC:

3298

AN:

10516

Middle Eastern (MID)

AF:

0.404

AC:

118

AN:

292

European-Non Finnish (NFE)

AF:

0.346

AC:

23547

AN:

67962

Other (OTH)

AF:

0.348

AC:

735

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1859

3718

5576

7435

9294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

574

1148

1722

2296

2870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.353

Hom.:

38772

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

Jul 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 29632382, 30012220, 29874175) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

(source)

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;.

PhyloP100

1.4

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

PromoterAI

-0.011

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.023

gMVP

0.45

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

1.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over