rs6762208

chr3-185613377-C-Achr3-185613377-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.39 (11937 hom., cov: 32)
  • Exomes 𝑓: 0.35 (90794 hom.)
• Consequence: SENP2 NM_021627.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.38

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
SENP2	NM_021627.3	c.902C>A	p.Thr301Lys	missense_variant	10/17	ENST00000296257.10
SENP2	XM_005247690.4	c.902C>A	p.Thr301Lys	missense_variant	10/16
SENP2	XM_005247691.4	c.557C>A	p.Thr186Lys	missense_variant	8/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SENP2	ENST00000296257.10	c.902C>A	p.Thr301Lys	missense_variant	10/17	1	NM_021627.3	P1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59355 AN: 151796 Hom.: 11932 Cov.: 32

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

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.: 27 AF XY: 0.356 AC XY: 251793 AN XY: 706454

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.: 32 AF XY: 0.394 AC XY: 29253 AN XY: 74258

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	T
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	N
LIST_S2	Benign	0.21	T;T
MetaRNN	Benign	0.000036	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-2.4	N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.44	T
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	T
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

Other links and lift over

dbSNP: rs6762208; hg19: chr3-185331165; COSMIC: COSV56194769; COSMIC: COSV56194769;