rs3093927

Variant names:

• chr14-20354936-G-A
• rs3093927
• NM_001042618.2:c.891G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001042618.2(PARP2):​c.891G>A​(p.Pro297Pro) 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
• Publications: 9 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PARP2	NM_001042618.2	c.891G>A	p.Pro297Pro	synonymous_variant	Exon 9 of 16	ENST00000429687.8	NP_001036083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP2	ENST00000429687.8	c.891G>A	p.Pro297Pro	synonymous_variant	Exon 9 of 16	1	NM_001042618.2	ENSP00000392972.3

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

GnomAD2 exomes AF: 0.0178 AC: 4437 AN: 248656 AF XY: 0.0147

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 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

African (AFR) AF: 0.193 AC: 6464 AN: 33426

American (AMR) AF: 0.0161 AC: 719 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.00996 AC: 260 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00584 AC: 503 AN: 86144

European-Finnish (FIN) AF: 0.000843 AC: 45 AN: 53406

Middle Eastern (MID) AF: 0.0243 AC: 140 AN: 5764

European-Non Finnish (NFE) AF: 0.00490 AC: 5447 AN: 1111560

Other (OTH) AF: 0.0168 AC: 1017 AN: 60364

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

African (AFR) AF: 0.187 AC: 7750 AN: 41474

American (AMR) AF: 0.0254 AC: 388 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4830

European-Finnish (FIN) AF: 0.000942 AC: 10 AN: 10616

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00562 AC: 382 AN: 68012

Other (OTH) AF: 0.0426 AC: 90 AN: 2114

Alfa AF: 0.0225 Hom.: 859

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
PhyloP100		-0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3093927; hg19: chr14-20823095;