rs1760912

Positions:

• chr14-20355375-A-T

Variant summary

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

The ENST00000429687.8(PARP2):​c.903-377A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 180,134 control chromosomes in the GnomAD database, including 20,273 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 0.46 (18148 hom., cov: 32)
  • Exomes 𝑓: 0.37 (2125 hom.)
• Consequence: PARP2 ENST00000429687.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP2	NM_001042618.2	c.903-377A>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.903-377A>T		intron_variant		1	NM_001042618.2	ENSP00000392972	P2

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70411 AN: 151914 Hom.: 18112 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.374 AC: 10512 AN: 28102 Hom.: 2125 Cov.: 0 AF XY: 0.373 AC XY: 5539 AN XY: 14842

Gnomad4 AFR exome AF: 0.718

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.336

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.317

Gnomad4 NFE exome AF: 0.353

Gnomad4 OTH exome AF: 0.373

GnomAD4 genome AF: 0.464 AC: 70506 AN: 152032 Hom.: 18148 Cov.: 32 AF XY: 0.461 AC XY: 34249 AN XY: 74322

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.433

Alfa AF: 0.426 Hom.: 1916

Bravo AF: 0.476

Asia WGS AF: 0.498 AC: 1733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	14
DANN	Benign	0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs1760912; hg19: chr14-20823534;