chr14-20351068-G-A

Variant names:

Variant summary

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

The NM_001042618.2(PARP2):c.443G>A(p.Ser148Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,614,066 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 32 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 29 hom. )

Consequence

PARP2
NM_001042618.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.332

Publications

7 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=0.002349466).

BP6

Variant 14-20351068-G-A is Benign according to our data. Variant chr14-20351068-G-A is described in ClinVar as Benign. ClinVar VariationId is 779651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.012 (1826/152314) while in subpopulation AFR AF = 0.0416 (1731/41566). AF 95% confidence interval is 0.04. There are 32 homozygotes in GnomAd4. There are 866 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 32 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042618.2. 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.443G>A	p.Ser148Asn	missense	Exon 6 of 16	NP_001036083.1
	PARP2	NM_005484.4		c.482G>A	p.Ser161Asn	missense	Exon 6 of 16	NP_005475.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PARP2	ENST00000429687.8	TSL:1 MANE Select	c.443G>A	p.Ser148Asn	missense	Exon 6 of 16	ENSP00000392972.3
PARP2	ENST00000250416.9	TSL:1	c.482G>A	p.Ser161Asn	missense	Exon 6 of 16	ENSP00000250416.5
PARP2	ENST00000925416.1		c.467G>A	p.Ser156Asn	missense	Exon 6 of 16	ENSP00000595475.1

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1823

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0417

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00907

GnomAD2 exomes

AF:

0.00301

AC:

751

AN:

249502

AF XY:

0.00224

show subpopulations

Gnomad AFR exome

AF:

0.0417

Gnomad AMR exome

AF:

0.00246

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00115

AC:

1687

AN:

1461752

Hom.:

Cov.:

AF XY:

0.000954

AC XY:

694

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.0391

AC:

1309

AN:

33470

American (AMR)

AF:

0.00253

AC:

113

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000531

AC:

AN:

1111910

Other (OTH)

AF:

0.00313

AC:

189

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

143

214

286

357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.0120

AC:

1826

AN:

152314

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

866

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0416

AC:

1731

AN:

41566

American (AMR)

AF:

0.00386

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68036

Other (OTH)

AF:

0.00898

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

180

270

360

450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00453

Hom.:

Bravo

AF:

0.0137

ESP6500AA

AF:

0.0361

AC:

137

ESP6500EA

AF:

0.000607

AC:

ExAC

AF:

0.00352

AC:

426

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.024

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.49

PhyloP100

0.33

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.050

REVEL

Benign

0.034

Sift

Benign

0.49

Sift4G

Benign

0.63

Polyphen

0.011

Vest4

0.11

MVP

0.28

MPC

0.095

ClinPred

0.0033

GERP RS

3.6

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

Varity_R

0.12

gMVP

0.24

Mutation Taster

=95/5

polymorphism

(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