rs3093905

chr14-20351068-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001042618.2(PARP2):c.443G>A(p.Ser148Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,614,066 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (29 hom.)
• Consequence: PARP2 NM_001042618.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.332

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002349466).
• BP6: Variant 14-20351068-G-A is Benign according to our data. Variant chr14-20351068-G-A is described in ClinVar as [Benign]. Clinvar id is 779651.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.012 (1826/152314) while in subpopulation AFR AF= 0.0416 (1731/41566). AF 95% confidence interval is 0.04. There are 32 homozygotes in gnomad4. There are 866 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP2	NM_001042618.2	c.443G>A	p.Ser148Asn	missense_variant	6/16	ENST00000429687.8
PARP2	NM_005484.4	c.482G>A	p.Ser161Asn	missense_variant	6/16
PARP2	XM_005267247.4	c.482G>A	p.Ser161Asn	missense_variant	6/15
PARP2	XM_017020912.2	c.443G>A	p.Ser148Asn	missense_variant	6/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP2	ENST00000429687.8	c.443G>A	p.Ser148Asn	missense_variant	6/16	1	NM_001042618.2	P2

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1823 AN: 152196 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.0417

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00907

GnomAD3 exomes AF: 0.00301 AC: 751 AN: 249502 Hom.: 14 AF XY: 0.00224 AC XY: 303 AN XY: 135374

Gnomad AFR exome AF: 0.0417

Gnomad AMR exome AF: 0.00246

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.00115 AC: 1687 AN: 1461752 Hom.: 29 Cov.: 30 AF XY: 0.000954 AC XY: 694 AN XY: 727186

Gnomad4 AFR exome AF: 0.0391

Gnomad4 AMR exome AF: 0.00253

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000531

Gnomad4 OTH exome AF: 0.00313

GnomAD4 genome AF: 0.0120 AC: 1826 AN: 152314 Hom.: 32 Cov.: 32 AF XY: 0.0116 AC XY: 866 AN XY: 74476

Gnomad4 AFR AF: 0.0416

Gnomad4 AMR AF: 0.00386

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.00260 Hom.: 10

Bravo AF: 0.0137

ESP6500AA AF: 0.0361 AC: 137

ESP6500EA AF: 0.000607 AC: 5

ExAC AF: 0.00352 AC: 426

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	16
Dann	Benign	0.94
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.74	T;T;T
MetaRNN	Benign	0.0023	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.59	D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.050	N;N;N
REVEL	Benign	0.034
Sift	Benign	0.49	T;T;T
Sift4G	Benign	0.63	T;T;T
Polyphen		0.011	B;B;.
Vest4		0.11
MVP		0.28
MPC		0.095
ClinPred		0.0033	T
GERP RS		3.6
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7
Varity_R		0.12
gMVP		0.24

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

Publications

LitVar

Other links and lift over

dbSNP: rs3093905; hg19: chr14-20819227;