dbSNP rs3093927: PARP2:p.Pro297Pro (chr14-20354936-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001042618.2(PARP2):c.891G>A(p.Pro297Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,613,232 control chromosomes in the GnomAD database, including 1,431 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 0.057 ( 757 hom., cov: 32)

Exomes 𝑓: 0.010 ( 674 hom. )

Consequence

PARP2
NM_001042618.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.179

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 made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP7

Synonymous conserved (PhyloP=-0.179 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP2	NM_001042618.2 link	c.891G>A	p.Pro297Pro	synonymous_variant	Exon 9 of 16	ENST00000429687.8	NP_001036083.1	Q9UGN5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP2	ENST00000429687.8 link	c.891G>A	p.Pro297Pro	synonymous_variant	Exon 9 of 16	1	NM_001042618.2	ENSP00000392972.3		Q9UGN5-2

Frequencies

GnomAD3 genomes

AF:

0.0570

AC:

8669

AN:

152076

Hom.:

756

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0254

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00562

Gnomad OTH

AF:

0.0430

GnomAD3 exomes

AF:

0.0178

AC:

4437

AN:

248656

Hom.:

299

AF XY:

0.0147

AC XY:

1978

AN XY:

134912

show subpopulations

Gnomad AFR exome

AF:

0.186

Gnomad AMR exome

AF:

0.0145

Gnomad ASJ exome

AF:

0.00829

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00574

Gnomad FIN exome

AF:

0.000790

Gnomad NFE exome

AF:

0.00610

Gnomad OTH exome

AF:

0.0166

GnomAD4 exome

AF:

0.00999

AC:

14595

AN:

1461038

Hom.:

674

Cov.:

AF XY:

0.00934

AC XY:

6787

AN XY:

726856

show subpopulations

Gnomad4 AFR exome

AF:

0.193

Gnomad4 AMR exome

AF:

0.0161

Gnomad4 ASJ exome

AF:

0.00996

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00584

Gnomad4 FIN exome

AF:

0.000843

Gnomad4 NFE exome

AF:

0.00490

Gnomad4 OTH exome

AF:

0.0168

GnomAD4 genome

AF:

0.0571

AC:

8683

AN:

152194

Hom.:

757

Cov.:

AF XY:

0.0559

AC XY:

4164

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.187

Gnomad4 AMR

AF:

0.0254

Gnomad4 ASJ

AF:

0.00836

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00562

Gnomad4 OTH

AF:

0.0426

Alfa

AF:

0.0128

Hom.:

221

Bravo

AF:

0.0642

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.00611

EpiControl

AF:

0.00605

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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