rs2297616

Variant names:

• chr14-20345130-G-A
• rs2297616
• NM_001042618.2:c.202+43G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005484.4(PARP2):​c.241+4G>A variant causes a splice 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.20 (3616 hom., cov: 32)
  • Exomes 𝑓: 0.25 (46839 hom.)
• Consequence: PARP2 NM_005484.4 splice_region, intron
• Scores: Splicing: ADA: 0.0002421
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 23 publications found

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]

ENSG00000254846 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.202+43G>A		intron	N/A	NP_001036083.1	Q9UGN5-2
	PARP2	NM_005484.4		c.241+4G>A		splice_region intron	N/A	NP_005475.2	Q9UGN5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP2	ENST00000429687.8	TSL:1 MANE Select	c.202+43G>A		intron	N/A	ENSP00000392972.3	Q9UGN5-2
	PARP2	ENST00000250416.9	TSL:1	c.241+4G>A		splice_region intron	N/A	ENSP00000250416.5	Q9UGN5-1
	PARP2	ENST00000925416.1		c.202+43G>A		intron	N/A	ENSP00000595475.1

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

GnomAD2 exomes AF: 0.246 AC: 60796 AN: 247442 AF XY: 0.251

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 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

African (AFR) AF: 0.0766 AC: 2547 AN: 33234

American (AMR) AF: 0.233 AC: 10263 AN: 44062

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 4983 AN: 25960

East Asian (EAS) AF: 0.194 AC: 7699 AN: 39654

South Asian (SAS) AF: 0.331 AC: 28491 AN: 85964

European-Finnish (FIN) AF: 0.285 AC: 15240 AN: 53390

Middle Eastern (MID) AF: 0.183 AC: 1050 AN: 5742

European-Non Finnish (NFE) AF: 0.252 AC: 278794 AN: 1104890

Other (OTH) AF: 0.235 AC: 14081 AN: 60034

GnomAD4 genome AF: 0.201 AC: 30609 AN: 152094 Hom.: 3616 Cov.: 32 AF XY: 0.202 AC XY: 15021 AN XY: 74334

African (AFR) AF: 0.0798 AC: 3314 AN: 41512

American (AMR) AF: 0.197 AC: 3015 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 710 AN: 3468

East Asian (EAS) AF: 0.192 AC: 991 AN: 5160

South Asian (SAS) AF: 0.344 AC: 1656 AN: 4814

European-Finnish (FIN) AF: 0.290 AC: 3064 AN: 10564

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17228 AN: 67980

Other (OTH) AF: 0.200 AC: 422 AN: 2108

Alfa AF: 0.231 Hom.: 7281

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.63
PhyloP100		0.075
Mutation Taster		=64/36	polymorphism (auto)

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

Other links and lift over

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