rs2297616

chr14-20345130-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000250416.9(PARP2):c.241+4G>A variant causes a splice donor region, 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 ENST00000250416.9 splice_donor_region, intron
• Scores: Splicing: ADA: 0.0002421
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750

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]

(HGNC:):

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP2	NM_001042618.2	c.202+43G>A		intron_variant		ENST00000429687.8
PARP2	NM_005484.4	c.241+4G>A		splice_donor_region_variant, intron_variant
PARP2	XM_005267247.4	c.241+4G>A		splice_donor_region_variant, intron_variant
PARP2	XM_017020912.2	c.202+43G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP2	ENST00000429687.8	c.202+43G>A		intron_variant		1	NM_001042618.2	P2
	ENST00000528210.1	n.325-754C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30608 AN: 151976 Hom.: 3619 Cov.: 32

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

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.: 29 AF XY: 0.253 AC XY: 182921 AN XY: 722802

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.: 32 AF XY: 0.202 AC XY: 15021 AN XY: 74334

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

Other links and lift over

dbSNP: rs2297616; hg19: chr14-20813289; COSMIC: COSV51639445; COSMIC: COSV51639445;