rs3093938

Variant names:

• chr14-20356935-A-G
• rs3093938
• NM_001042618.2:c.1330-116A>G

Variant summary

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

The ENST00000429687.8(PARP2):​c.1330-116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 758,856 control chromosomes in the GnomAD database, including 526 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 0.037 (357 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (169 hom.)
• Consequence: PARP2 ENST00000429687.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 2 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000429687.8. 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.1330-116A>G		intron	N/A	NP_001036083.1
	PARP2	NM_005484.4		c.1369-116A>G		intron	N/A	NP_005475.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP2	ENST00000429687.8	TSL:1 MANE Select	c.1330-116A>G		intron	N/A	ENSP00000392972.3
	PARP2	ENST00000250416.9	TSL:1	c.1369-116A>G		intron	N/A	ENSP00000250416.5
	PARP2	ENST00000527915.5	TSL:2	c.1369-116A>G		intron	N/A	ENSP00000432283.1

Frequencies

GnomAD3 genomes AF: 0.0367 AC: 5576 AN: 152122 Hom.: 347 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.0311

GnomAD4 exome AF: 0.00562 AC: 3407 AN: 606616 Hom.: 169 Cov.: 8 AF XY: 0.00470 AC XY: 1523 AN XY: 324174

African (AFR) AF: 0.130 AC: 2140 AN: 16400

American (AMR) AF: 0.00930 AC: 321 AN: 34500

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 243 AN: 18332

East Asian (EAS) AF: 0.00 AC: 0 AN: 33346

South Asian (SAS) AF: 0.000380 AC: 23 AN: 60586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45810

Middle Eastern (MID) AF: 0.0121 AC: 48 AN: 3968

European-Non Finnish (NFE) AF: 0.000594 AC: 215 AN: 361790

Other (OTH) AF: 0.0131 AC: 417 AN: 31884

GnomAD4 genome AF: 0.0369 AC: 5621 AN: 152240 Hom.: 357 Cov.: 32 AF XY: 0.0360 AC XY: 2679 AN XY: 74462

African (AFR) AF: 0.126 AC: 5249 AN: 41510

American (AMR) AF: 0.0142 AC: 217 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 38 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000706 AC: 48 AN: 68010

Other (OTH) AF: 0.0307 AC: 65 AN: 2114

Alfa AF: 0.0482 Hom.: 59

Bravo AF: 0.0420

Asia WGS AF: 0.0140 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.68
PhyloP100		-0.30
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: rs3093938; hg19: chr14-20825094;