dbSNP rs2700: PARP2:c.*9A>C (chr14-20357806-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001042618.2(PARP2):c.*9A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,607,518 control chromosomes in the GnomAD database, including 65,395 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4699 hom., cov: 32)

Exomes 𝑓: 0.29 ( 60696 hom. )

Consequence

PARP2
NM_001042618.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.155

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP2	NM_001042618.2 link	c.*9A>C		3_prime_UTR_variant	Exon 16 of 16	ENST00000429687.8	NP_001036083.1	Q9UGN5-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PARP2	ENST00000429687.8 link	c.*9A>C	3_prime_UTR_variant	Exon 16 of 16	1	NM_001042618.2	ENSP00000392972.3	Q9UGN5-2
PARP2	ENST00000250416.9 link	c.*9A>C	3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000250416.5	Q9UGN5-1
PARP2	ENST00000527915.5 link	c.*282A>C	3_prime_UTR_variant	Exon 15 of 15	2		ENSP00000432283.1	G3V167
PARP2	ENST00000539930.1 link	c.*133A>C	downstream_gene_variant		3		ENSP00000445524.1	H0YH02

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35141

AN:

152060

Hom.:

4703

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0940

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.358

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.243

GnomAD2 exomes

AF:

0.280

AC:

68499

AN:

244884

AF XY:

0.285

show subpopulations

Gnomad AFR exome

AF:

0.0897

Gnomad AMR exome

AF:

0.262

Gnomad ASJ exome

AF:

0.258

Gnomad EAS exome

AF:

0.277

Gnomad FIN exome

AF:

0.307

Gnomad NFE exome

AF:

0.289

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.286

AC:

416019

AN:

1455340

Hom.:

60696

Cov.:

AF XY:

0.288

AC XY:

208675

AN XY:

723900

show subpopulations

Gnomad4 AFR exome

AF:

0.0915

AC:

3039

AN:

33202

Gnomad4 AMR exome

AF:

0.253

AC:

11007

AN:

43488

Gnomad4 ASJ exome

AF:

0.253

AC:

6584

AN:

26056

Gnomad4 EAS exome

AF:

0.271

AC:

10752

AN:

39670

Gnomad4 SAS exome

AF:

0.344

AC:

29320

AN:

85138

Gnomad4 FIN exome

AF:

0.304

AC:

16250

AN:

53396

Gnomad4 NFE exome

AF:

0.290

AC:

321201

AN:

1108434

Gnomad4 Remaining exome

AF:

0.272

AC:

16391

AN:

60202

Heterozygous variant carriers

14723

29446

44169

58892

73615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

10592

21184

31776

42368

52960

<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:

0.231

AC:

35140

AN:

152178

Hom.:

4699

Cov.:

AF XY:

0.231

AC XY:

17217

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0939

AC:

0.0938673

AN:

0.0938673

Gnomad4 AMR

AF:

0.226

AC:

0.225739

AN:

0.225739

Gnomad4 ASJ

AF:

0.261

AC:

0.261095

AN:

0.261095

Gnomad4 EAS

AF:

0.278

AC:

0.277606

AN:

0.277606

Gnomad4 SAS

AF:

0.358

AC:

0.357735

AN:

0.357735

Gnomad4 FIN

AF:

0.306

AC:

0.305545

AN:

0.305545

Gnomad4 NFE

AF:

0.291

AC:

0.290506

AN:

0.290506

Gnomad4 OTH

AF:

0.244

AC:

0.244087

AN:

0.244087

Heterozygous variant carriers

1381

2761

4142

5522

6903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<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:

0.260

Hom.:

8894

Bravo

AF:

0.218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

8.2

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

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