Genetic Variant PARP2:p.Arg13Gly (chr14-20343678-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001042618.2(PARP2):c.37A>G(p.Arg13Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PARP2
NM_001042618.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.19

Variant links:

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]

PARP2 links:

ENSG00000259001 (HGNC:):

ENSG00000259001 links:

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ACMG classification

Classification made for transcript

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=0.07821703).

BP6

Variant 14-20343678-A-G is Benign according to our data. Variant chr14-20343678-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2519693.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP2	NM_001042618.2 link	c.37A>G	p.Arg13Gly	missense_variant	Exon 1 of 16	ENST00000429687.8	NP_001036083.1	Q9UGN5-2
PARP2	NM_005484.4 link	c.37A>G	p.Arg13Gly	missense_variant	Exon 1 of 16		NP_005475.2	Q9UGN5-1
PARP2	XM_005267247.4 link	c.37A>G	p.Arg13Gly	missense_variant	Exon 1 of 15		XP_005267304.1
PARP2	XM_017020912.2 link	c.37A>G	p.Arg13Gly	missense_variant	Exon 1 of 15		XP_016876401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP2	ENST00000429687.8 link	c.37A>G	p.Arg13Gly	missense_variant	Exon 1 of 16	1	NM_001042618.2	ENSP00000392972.3		Q9UGN5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1457448

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724520

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 24, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.35

DANN

Benign

0.48

DEOGEN2

Benign

0.069

.;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00019

LIST_S2

Benign

0.46

T;T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.078

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

N;N;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.040

Sift

Benign

0.40

T;T;T

Sift4G

Benign

0.085

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.22

MutPred

0.32

Loss of methylation at R13 (P = 8e-04);Loss of methylation at R13 (P = 8e-04);Loss of methylation at R13 (P = 8e-04);

MVP

0.20

MPC

0.13

ClinPred

0.062

GERP RS

-9.6

Varity_R

0.045

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over