14-20354149-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005484.4(PARP2):c.704A>G(p.Asp235Gly) variant causes a missense change. The variant allele was found at a frequency of 0.02 in 1,612,584 control chromosomes in the GnomAD database, including 470 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D235V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.019 ( 49 hom., cov: 32)

Exomes 𝑓: 0.020 ( 421 hom. )

Consequence

PARP2
NM_005484.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.06

Publications

21 publications found

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:

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=0.003672868).

BP6

Variant 14-20354149-A-G is Benign according to our data. Variant chr14-20354149-A-G is described in ClinVar as Benign. ClinVar VariationId is 1230992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0186 (2835/152294) while in subpopulation NFE AF = 0.0244 (1659/68026). AF 95% confidence interval is 0.0234. There are 49 homozygotes in GnomAd4. There are 1519 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005484.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP2	NM_001042618.2	MANE Select	c.665A>G	p.Asp222Gly	missense	Exon 8 of 16	NP_001036083.1
	PARP2	NM_005484.4		c.704A>G	p.Asp235Gly	missense	Exon 8 of 16	NP_005475.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PARP2	ENST00000429687.8	TSL:1 MANE Select	c.665A>G	p.Asp222Gly	missense	Exon 8 of 16	ENSP00000392972.3
PARP2	ENST00000250416.9	TSL:1	c.704A>G	p.Asp235Gly	missense	Exon 8 of 16	ENSP00000250416.5
PARP2	ENST00000925416.1		c.689A>G	p.Asp230Gly	missense	Exon 8 of 16	ENSP00000595475.1

Frequencies

GnomAD3 genomes

AF:

0.0186

AC:

2835

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0726

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0244

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.0193

AC:

4817

AN:

249530

AF XY:

0.0190

show subpopulations

Gnomad AFR exome

AF:

0.00284

Gnomad AMR exome

AF:

0.00704

Gnomad ASJ exome

AF:

0.0185

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0675

Gnomad NFE exome

AF:

0.0242

Gnomad OTH exome

AF:

0.0195

GnomAD4 exome

AF:

0.0201

AC:

29389

AN:

1460290

Hom.:

421

Cov.:

AF XY:

0.0195

AC XY:

14203

AN XY:

726558

show subpopulations

African (AFR)

AF:

0.00290

AC:

AN:

33450

American (AMR)

AF:

0.00686

AC:

307

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0160

AC:

418

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39672

South Asian (SAS)

AF:

0.000905

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.0662

AC:

3536

AN:

53410

Middle Eastern (MID)

AF:

0.00850

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0215

AC:

23848

AN:

1110582

Other (OTH)

AF:

0.0175

AC:

1056

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

1284

2569

3853

5138

6422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

824

1648

2472

3296

4120

<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:

0.0186

AC:

2835

AN:

152294

Hom.:

Cov.:

AF XY:

0.0204

AC XY:

1519

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00265

AC:

110

AN:

41578

American (AMR)

AF:

0.0109

AC:

166

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0726

AC:

770

AN:

10600

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0244

AC:

1659

AN:

68026

Other (OTH)

AF:

0.0152

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

145

290

435

580

725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0196

Hom.:

157

Bravo

AF:

0.0133

TwinsUK

AF:

0.0156

AC:

ALSPAC

AF:

0.0174

AC:

ESP6500AA

AF:

0.00243

AC:

ESP6500EA

AF:

0.0230

AC:

189

ExAC

AF:

0.0194

AC:

2342

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0195

EpiControl

AF:

0.0168

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.3

PhyloP100

7.1

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.17

Sift

Benign

0.032

Sift4G

Benign

0.098

Polyphen

0.36

Vest4

0.18

MPC

0.38

ClinPred

0.066

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.80

gMVP

0.51

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over