rs1760912

Variant names:

• chr14-20355375-A-T
• rs1760912
• NM_001042618.2:c.903-377A>T

Variant summary

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

The NM_001042618.2(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 NM_001042618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP2	NM_001042618.2	MANE Select	c.903-377A>T		intron	N/A	NP_001036083.1	Q9UGN5-2
	PARP2	NM_005484.4		c.942-377A>T		intron	N/A	NP_005475.2	Q9UGN5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP2	ENST00000429687.8	TSL:1 MANE Select	c.903-377A>T		intron	N/A	ENSP00000392972.3	Q9UGN5-2
	PARP2	ENST00000250416.9	TSL:1	c.942-377A>T		intron	N/A	ENSP00000250416.5	Q9UGN5-1
	PARP2	ENST00000925416.1		c.927-377A>T		intron	N/A	ENSP00000595475.1

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

African (AFR) AF: 0.718 AC: 577 AN: 804

American (AMR) AF: 0.413 AC: 930 AN: 2250

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 300 AN: 922

East Asian (EAS) AF: 0.336 AC: 495 AN: 1474

South Asian (SAS) AF: 0.493 AC: 766 AN: 1554

European-Finnish (FIN) AF: 0.317 AC: 261 AN: 824

Middle Eastern (MID) AF: 0.340 AC: 34 AN: 100

European-Non Finnish (NFE) AF: 0.353 AC: 6535 AN: 18526

Other (OTH) AF: 0.373 AC: 614 AN: 1648

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

African (AFR) AF: 0.704 AC: 29210 AN: 41464

American (AMR) AF: 0.409 AC: 6239 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1137 AN: 3470

East Asian (EAS) AF: 0.362 AC: 1874 AN: 5176

South Asian (SAS) AF: 0.526 AC: 2532 AN: 4818

European-Finnish (FIN) AF: 0.361 AC: 3817 AN: 10562

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24401 AN: 67970

Other (OTH) AF: 0.433 AC: 911 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	14
DANN	Benign	0.25
PhyloP100		0.61
PromoterAI		-0.018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1760912; hg19: chr14-20823534;