Genetic Variant NM_001042618.2:c.202+43G>A (chr14-20345130-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001042618.2(PARP2):c.202+43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,605,024 control chromosomes in the GnomAD database, including 50,455 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 0.20 ( 3616 hom., cov: 32)

Exomes 𝑓: 0.25 ( 46839 hom. )

Consequence

PARP2
NM_001042618.2 intron

Scores

Splicing: ADA: 0.0002421

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0750

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:

ENSG00000254846 (HGNC:):

ENSG00000254846 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PARP2	NM_001042618.2 link	c.202+43G>A	intron_variant	Intron 2 of 15	ENST00000429687.8	NP_001036083.1	Q9UGN5-2
PARP2	NM_005484.4 link	c.241+4G>A	splice_region_variant, intron_variant	Intron 2 of 15		NP_005475.2	Q9UGN5-1
PARP2	XM_005267247.4 link	c.241+4G>A	splice_region_variant, intron_variant	Intron 2 of 14		XP_005267304.1
PARP2	XM_017020912.2 link	c.202+43G>A	intron_variant	Intron 2 of 14		XP_016876401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP2	ENST00000429687.8 link	c.202+43G>A		intron_variant	Intron 2 of 15	1	NM_001042618.2	ENSP00000392972.3		Q9UGN5-2

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30608

AN:

151976

Hom.:

3619

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0800

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.344

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.199

GnomAD3 exomes

AF:

0.246

AC:

60796

AN:

247442

Hom.:

8000

AF XY:

0.251

AC XY:

33700

AN XY:

134368

show subpopulations

Gnomad AFR exome

AF:

0.0765

Gnomad AMR exome

AF:

0.242

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.188

Gnomad SAS exome

AF:

0.335

Gnomad FIN exome

AF:

0.288

Gnomad NFE exome

AF:

0.251

Gnomad OTH exome

AF:

0.248

GnomAD4 exome

AF:

0.250

AC:

363148

AN:

1452930

Hom.:

46839

Cov.:

AF XY:

0.253

AC XY:

182921

AN XY:

722802

show subpopulations

Gnomad4 AFR exome

AF:

0.0766

Gnomad4 AMR exome

AF:

0.233

Gnomad4 ASJ exome

AF:

0.192

Gnomad4 EAS exome

AF:

0.194

Gnomad4 SAS exome

AF:

0.331

Gnomad4 FIN exome

AF:

0.285

Gnomad4 NFE exome

AF:

0.252

Gnomad4 OTH exome

AF:

0.235

GnomAD4 genome

AF:

0.201

AC:

30609

AN:

152094

Hom.:

3616

Cov.:

AF XY:

0.202

AC XY:

15021

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0798

Gnomad4 AMR

AF:

0.197

Gnomad4 ASJ

AF:

0.205

Gnomad4 EAS

AF:

0.192

Gnomad4 SAS

AF:

0.344

Gnomad4 FIN

AF:

0.290

Gnomad4 NFE

AF:

0.253

Gnomad4 OTH

AF:

0.200

Alfa

AF:

0.235

Hom.:

5579

Bravo

AF:

0.186

Asia WGS

AF:

0.264

AC:

919

AN:

3478

EpiCase

AF:

0.241

EpiControl

AF:

0.233

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.1

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00024

dbscSNV1_RF

Benign

0.080

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