Variant rs3093926 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001042618.2(PARP2):c.848G>A(p.Arg283Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0561 in 1,613,510 control chromosomes in the GnomAD database, including 2,935 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.042 ( 194 hom., cov: 32)

Exomes 𝑓: 0.058 ( 2741 hom. )

Consequence

PARP2
NM_001042618.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.76

Variant links:

Genes affected

PARP2 (HGNC:272): (poly(ADP-ribose) polymerase 2) This gene encodes poly(ADP-ribosyl)transferase-like 2 protein, which contains a catalytic domain and is capable of catalyzing a poly(ADP-ribosyl)ation reaction. This protein has a catalytic domain which is homologous to that of poly (ADP-ribosyl) transferase, but lacks an N-terminal DNA binding domain which activates the C-terminal catalytic domain of poly (ADP-ribosyl) transferase. The basic residues within the N-terminal region of this protein may bear potential DNA-binding properties, and may be involved in the nuclear and/or nucleolar targeting of the protein. Two alternatively spliced transcript variants encoding distinct isoforms have been found. [provided by RefSeq, Jul 2008]

PARP2 links:

PARP2 (HGNC:):

PARP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00636518).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP2	NM_001042618.2 linkuse as main transcript	c.848G>A	p.Arg283Gln	missense_variant	9/16	ENST00000429687.8	NP_001036083.1	Q9UGN5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP2	ENST00000429687.8 linkuse as main transcript	c.848G>A	p.Arg283Gln	missense_variant	9/16	1	NM_001042618.2	ENSP00000392972.3		Q9UGN5-2

Frequencies

GnomAD3 genomes

AF:

0.0419

AC:

6368

AN:

152004

Hom.:

194

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.0496

Gnomad ASJ

AF:

0.0559

Gnomad EAS

AF:

0.00213

Gnomad SAS

AF:

0.0330

Gnomad FIN

AF:

0.0142

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0644

Gnomad OTH

AF:

0.0535

GnomAD3 exomes

AF:

0.0426

AC:

10617

AN:

249380

Hom.:

312

AF XY:

0.0443

AC XY:

5996

AN XY:

135302

show subpopulations

Gnomad AFR exome

AF:

0.0106

Gnomad AMR exome

AF:

0.0328

Gnomad ASJ exome

AF:

0.0605

Gnomad EAS exome

AF:

0.000445

Gnomad SAS exome

AF:

0.0366

Gnomad FIN exome

AF:

0.0159

Gnomad NFE exome

AF:

0.0614

Gnomad OTH exome

AF:

0.0491

GnomAD4 exome

AF:

0.0576

AC:

84152

AN:

1461390

Hom.:

2741

Cov.:

AF XY:

0.0573

AC XY:

41659

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.00935

Gnomad4 AMR exome

AF:

0.0351

Gnomad4 ASJ exome

AF:

0.0645

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.0363

Gnomad4 FIN exome

AF:

0.0169

Gnomad4 NFE exome

AF:

0.0653

Gnomad4 OTH exome

AF:

0.0585

GnomAD4 genome

AF:

0.0418

AC:

6366

AN:

152120

Hom.:

194

Cov.:

AF XY:

0.0391

AC XY:

2907

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0116

Gnomad4 AMR

AF:

0.0495

Gnomad4 ASJ

AF:

0.0559

Gnomad4 EAS

AF:

0.00194

Gnomad4 SAS

AF:

0.0330

Gnomad4 FIN

AF:

0.0142

Gnomad4 NFE

AF:

0.0644

Gnomad4 OTH

AF:

0.0530

Alfa

AF:

0.0601

Hom.:

558

Bravo

AF:

0.0453

TwinsUK

AF:

0.0723

AC:

268

ALSPAC

AF:

0.0620

AC:

239

ESP6500AA

AF:

0.0120

AC:

ESP6500EA

AF:

0.0644

AC:

538

ExAC

AF:

0.0408

AC:

4937

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

.;T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.77

T;T;T

MetaRNN

Benign

0.0064

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

.;L;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.045

Sift

Benign

0.10

T;T;T

Sift4G

Benign

0.12

T;T;T

Polyphen

0.16

B;B;.

Vest4

0.040

MPC

0.12

ClinPred

0.0094

GERP RS

3.8

Varity_R

0.35

gMVP

0.24

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over