NM_001042618.2:c.*9A>C

Variant names:

• chr14-20357806-A-C
• rs2700
• NM_001042618.2:c.*9A>C

Variant summary

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

The NM_001042618.2(PARP2):​c.*9A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,607,518 control chromosomes in the GnomAD database, including 65,395 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 0.23 (4699 hom., cov: 32)
  • Exomes 𝑓: 0.29 (60696 hom.)
• Consequence: PARP2 NM_001042618.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• 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 (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP2	NM_001042618.2	c.*9A>C		3_prime_UTR_variant	Exon 16 of 16	ENST00000429687.8	NP_001036083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP2	ENST00000429687.8	c.*9A>C		3_prime_UTR_variant	Exon 16 of 16	1	NM_001042618.2	ENSP00000392972.3
PARP2	ENST00000250416.9	c.*9A>C		3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000250416.5
PARP2	ENST00000527915.5	c.*282A>C		3_prime_UTR_variant	Exon 15 of 15	2		ENSP00000432283.1
PARP2	ENST00000539930.1	c.*133A>C		downstream_gene_variant		3		ENSP00000445524.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35141 AN: 152060 Hom.: 4703 Cov.: 32

Gnomad AFR AF: 0.0940

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.243

GnomAD2 exomes AF: 0.280 AC: 68499 AN: 244884 AF XY: 0.285

Gnomad AFR exome AF: 0.0897

Gnomad AMR exome AF: 0.262

Gnomad ASJ exome AF: 0.258

Gnomad EAS exome AF: 0.277

Gnomad FIN exome AF: 0.307

Gnomad NFE exome AF: 0.289

Gnomad OTH exome AF: 0.287

GnomAD4 exome AF: 0.286 AC: 416019 AN: 1455340 Hom.: 60696 Cov.: 31 AF XY: 0.288 AC XY: 208675 AN XY: 723900

African (AFR) AF: 0.0915 AC: 3039 AN: 33202

American (AMR) AF: 0.253 AC: 11007 AN: 43488

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 6584 AN: 26056

East Asian (EAS) AF: 0.271 AC: 10752 AN: 39670

South Asian (SAS) AF: 0.344 AC: 29320 AN: 85138

European-Finnish (FIN) AF: 0.304 AC: 16250 AN: 53396

Middle Eastern (MID) AF: 0.256 AC: 1475 AN: 5754

European-Non Finnish (NFE) AF: 0.290 AC: 321201 AN: 1108434

Other (OTH) AF: 0.272 AC: 16391 AN: 60202

GnomAD4 genome AF: 0.231 AC: 35140 AN: 152178 Hom.: 4699 Cov.: 32 AF XY: 0.231 AC XY: 17217 AN XY: 74382

African (AFR) AF: 0.0939 AC: 3900 AN: 41548

American (AMR) AF: 0.226 AC: 3452 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 906 AN: 3470

East Asian (EAS) AF: 0.278 AC: 1438 AN: 5180

South Asian (SAS) AF: 0.358 AC: 1725 AN: 4822

European-Finnish (FIN) AF: 0.306 AC: 3229 AN: 10568

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19748 AN: 67978

Other (OTH) AF: 0.244 AC: 516 AN: 2114

Alfa AF: 0.260 Hom.: 8894

Bravo AF: 0.218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.2
DANN	Benign	0.56
PhyloP100		-0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs2700; hg19: chr14-20825965; COSMIC: COSV51639486; COSMIC: COSV51639486;