14-20354893-G-A

Variant names:

• chr14-20354893-G-A
• rs3093926
• NM_001042618.2:c.848G>A

Variant summary

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

The NM_001042618.2(PARP2):​c.848G>A​(p.Arg283Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0561 in 1,613,510 control chromosomes in the GnomAD database, including 2,935 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.042 (194 hom., cov: 32)
  • Exomes 𝑓: 0.058 (2741 hom.)
• Consequence: PARP2 NM_001042618.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.76
• Publications: 26 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00636518).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0628 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042618.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP2	NM_001042618.2	MANE Select	c.848G>A	p.Arg283Gln	missense	Exon 9 of 16	NP_001036083.1
	PARP2	NM_005484.4		c.887G>A	p.Arg296Gln	missense	Exon 9 of 16	NP_005475.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP2	ENST00000429687.8	TSL:1 MANE Select	c.848G>A	p.Arg283Gln	missense	Exon 9 of 16	ENSP00000392972.3
	PARP2	ENST00000250416.9	TSL:1	c.887G>A	p.Arg296Gln	missense	Exon 9 of 16	ENSP00000250416.5
	PARP2	ENST00000527915.5	TSL:2	c.887G>A	p.Arg296Gln	missense	Exon 9 of 15	ENSP00000432283.1

Frequencies

GnomAD3 genomes AF: 0.0419 AC: 6368 AN: 152004 Hom.: 194 Cov.: 32

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0496

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.00213

Gnomad SAS AF: 0.0330

Gnomad FIN AF: 0.0142

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0644

Gnomad OTH AF: 0.0535

GnomAD2 exomes AF: 0.0426 AC: 10617 AN: 249380 AF XY: 0.0443

Gnomad AFR exome AF: 0.0106

Gnomad AMR exome AF: 0.0328

Gnomad ASJ exome AF: 0.0605

Gnomad EAS exome AF: 0.000445

Gnomad FIN exome AF: 0.0159

Gnomad NFE exome AF: 0.0614

Gnomad OTH exome AF: 0.0491

GnomAD4 exome AF: 0.0576 AC: 84152 AN: 1461390 Hom.: 2741 Cov.: 31 AF XY: 0.0573 AC XY: 41659 AN XY: 727024

African (AFR) AF: 0.00935 AC: 313 AN: 33478

American (AMR) AF: 0.0351 AC: 1568 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.0645 AC: 1684 AN: 26124

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39694

South Asian (SAS) AF: 0.0363 AC: 3132 AN: 86234

European-Finnish (FIN) AF: 0.0169 AC: 901 AN: 53418

Middle Eastern (MID) AF: 0.0812 AC: 468 AN: 5766

European-Non Finnish (NFE) AF: 0.0653 AC: 72545 AN: 1111618

Other (OTH) AF: 0.0585 AC: 3529 AN: 60376

GnomAD4 genome AF: 0.0418 AC: 6366 AN: 152120 Hom.: 194 Cov.: 32 AF XY: 0.0391 AC XY: 2907 AN XY: 74352

African (AFR) AF: 0.0116 AC: 480 AN: 41496

American (AMR) AF: 0.0495 AC: 756 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3472

East Asian (EAS) AF: 0.00194 AC: 10 AN: 5158

South Asian (SAS) AF: 0.0330 AC: 159 AN: 4812

European-Finnish (FIN) AF: 0.0142 AC: 150 AN: 10594

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0644 AC: 4377 AN: 67992

Other (OTH) AF: 0.0530 AC: 112 AN: 2114

Alfa AF: 0.0573 Hom.: 733

Bravo AF: 0.0453

TwinsUK AF: 0.0723 AC: 268

ALSPAC AF: 0.0620 AC: 239

ESP6500AA AF: 0.0120 AC: 48

ESP6500EA AF: 0.0644 AC: 538

ExAC AF: 0.0408 AC: 4937

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.0064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.8
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.045
Sift	Benign	0.10	T
Sift4G	Benign	0.12	T
Polyphen		0.16	B
Vest4		0.040
MPC		0.12
ClinPred		0.0094	T
GERP RS		3.8
Varity_R		0.35
gMVP		0.24
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3093926; hg19: chr14-20823052; COSMIC: COSV51638365; COSMIC: COSV51638365;