rs3093906

chr14-20351089-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001042618.2(PARP2):c.464A>G(p.Asn155Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000836 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.00023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000068 (0 hom.)
• Consequence: PARP2 NM_001042618.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.30

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04030326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP2	NM_001042618.2	c.464A>G	p.Asn155Ser	missense_variant	6/16	ENST00000429687.8
PARP2	NM_005484.4	c.503A>G	p.Asn168Ser	missense_variant	6/16
PARP2	XM_005267247.4	c.503A>G	p.Asn168Ser	missense_variant	6/15
PARP2	XM_017020912.2	c.464A>G	p.Asn155Ser	missense_variant	6/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP2	ENST00000429687.8	c.464A>G	p.Asn155Ser	missense_variant	6/16	1	NM_001042618.2	P2

Frequencies

GnomAD3 genomes AF: 0.000223 AC: 34 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000124 AC: 31 AN: 249518 Hom.: 0 AF XY: 0.000148 AC XY: 20 AN XY: 135386

Gnomad AFR exome AF: 0.000581

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.000458

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000684 AC: 100 AN: 1461738 Hom.: 0 Cov.: 30 AF XY: 0.0000866 AC XY: 63 AN XY: 727184

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000180

Gnomad4 OTH exome AF: 0.0000828

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152310 Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19 AN XY: 74492

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000857 Hom.: 0

Bravo AF: 0.000242

ESP6500AA AF: 0.000531 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000132 AC: 16

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	22
Dann	Uncertain	0.98
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.068
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.040	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.84	N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.72	N;N;N
REVEL	Benign	0.069
Sift	Benign	0.42	T;T;T
Sift4G	Benign	0.66	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.21
MVP		0.39
MPC		0.081
ClinPred		0.023	T
GERP RS		5.3
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.15
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3093906; hg19: chr14-20819248; COSMIC: COSV105859680; COSMIC: COSV105859680;