rs3093933

Positions:

• chr14-20356256-G-T

Variant summary

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

The NM_001042618.2(PARP2):​c.1102-51G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,597,880 control chromosomes in the GnomAD database, including 49,171 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 (3659 hom., cov: 32)
  • Exomes 𝑓: 0.25 (45512 hom.)
• Consequence: PARP2 NM_001042618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• 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	Protein	UniProt
PARP2	NM_001042618.2	c.1102-51G>T		intron_variant		ENST00000429687.8	NP_001036083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP2	ENST00000429687.8	c.1102-51G>T		intron_variant		1	NM_001042618.2	ENSP00000392972.3

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30993 AN: 151920 Hom.: 3660 Cov.: 32

Gnomad AFR AF: 0.0904

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.206

GnomAD3 exomes AF: 0.247 AC: 60379 AN: 244114 Hom.: 8024 AF XY: 0.252 AC XY: 33319 AN XY: 132470

Gnomad AFR exome AF: 0.0870

Gnomad AMR exome AF: 0.234

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.269

Gnomad SAS exome AF: 0.330

Gnomad FIN exome AF: 0.283

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.248

GnomAD4 exome AF: 0.247 AC: 356770 AN: 1445844 Hom.: 45512 Cov.: 30 AF XY: 0.250 AC XY: 179464 AN XY: 718924

Gnomad4 AFR exome AF: 0.0870

Gnomad4 AMR exome AF: 0.227

Gnomad4 ASJ exome AF: 0.195

Gnomad4 EAS exome AF: 0.261

Gnomad4 SAS exome AF: 0.327

Gnomad4 FIN exome AF: 0.281

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.204 AC: 30996 AN: 152036 Hom.: 3659 Cov.: 32 AF XY: 0.205 AC XY: 15255 AN XY: 74288

Gnomad4 AFR AF: 0.0902

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.207

Alfa AF: 0.236 Hom.: 9236

Bravo AF: 0.190

Asia WGS AF: 0.288 AC: 1003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.41

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

LitVar

Other links and lift over

dbSNP: rs3093933; hg19: chr14-20824415; COSMIC: COSV51639476; COSMIC: COSV51639476;