rs3093927

Positions:

• chr14-20354936-G-A
• chr14-20354936-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001042618.2(PARP2):​c.891G>A​(p.Pro297=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,613,232 control chromosomes in the GnomAD database, including 1,431 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 0.057 (757 hom., cov: 32)
  • Exomes 𝑓: 0.010 (674 hom.)
• Consequence: PARP2 NM_001042618.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=-0.179 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP2	NM_001042618.2	c.891G>A	p.Pro297=	synonymous_variant	9/16	ENST00000429687.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP2	ENST00000429687.8	c.891G>A	p.Pro297=	synonymous_variant	9/16	1	NM_001042618.2	P2

Frequencies

GnomAD3 genomes AF: 0.0570 AC: 8669 AN: 152076 Hom.: 756 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0254

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00562

Gnomad OTH AF: 0.0430

GnomAD3 exomes AF: 0.0178 AC: 4437 AN: 248656 Hom.: 299 AF XY: 0.0147 AC XY: 1978 AN XY: 134912

Gnomad AFR exome AF: 0.186

Gnomad AMR exome AF: 0.0145

Gnomad ASJ exome AF: 0.00829

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00574

Gnomad FIN exome AF: 0.000790

Gnomad NFE exome AF: 0.00610

Gnomad OTH exome AF: 0.0166

GnomAD4 exome AF: 0.00999 AC: 14595 AN: 1461038 Hom.: 674 Cov.: 31 AF XY: 0.00934 AC XY: 6787 AN XY: 726856

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.0161

Gnomad4 ASJ exome AF: 0.00996

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00584

Gnomad4 FIN exome AF: 0.000843

Gnomad4 NFE exome AF: 0.00490

Gnomad4 OTH exome AF: 0.0168

GnomAD4 genome AF: 0.0571 AC: 8683 AN: 152194 Hom.: 757 Cov.: 32 AF XY: 0.0559 AC XY: 4164 AN XY: 74432

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.0254

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.000942

Gnomad4 NFE AF: 0.00562

Gnomad4 OTH AF: 0.0426

Alfa AF: 0.0128 Hom.: 221

Bravo AF: 0.0642

Asia WGS AF: 0.0140 AC: 47 AN: 3478

EpiCase AF: 0.00611

EpiControl AF: 0.00605

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3093927; hg19: chr14-20823095;