Variant chr14-20346890-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001042618.2(PARP2):c.301G>A(p.Val101Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,692 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PARP2
NM_001042618.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.43

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2646036).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PARP2	NM_001042618.2 linkuse as main transcript	c.301G>A	p.Val101Ile	missense_variant	4/16	ENST00000429687.8
PARP2	NM_005484.4 linkuse as main transcript	c.340G>A	p.Val114Ile	missense_variant	4/16
PARP2	XM_005267247.4 linkuse as main transcript	c.340G>A	p.Val114Ile	missense_variant	4/15
PARP2	XM_017020912.2 linkuse as main transcript	c.301G>A	p.Val101Ile	missense_variant	4/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP2	ENST00000429687.8 linkuse as main transcript	c.301G>A	p.Val101Ile	missense_variant	4/16	1	NM_001042618.2	P2	Q9UGN5-2
	ENST00000528210.1 linkuse as main transcript			upstream_gene_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000803

AC:

AN:

249012

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135176

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1454692

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724218

show subpopulations

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:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2023

The c.340G>A (p.V114I) alteration is located in exon 4 (coding exon 4) of the PARP2 gene. This alteration results from a G to A substitution at nucleotide position 340, causing the valine (V) at amino acid position 114 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

0.024

Eigen_PC

Benign

0.084

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.0048

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.37

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.38

T;T;T

Polyphen

1.0

D;D;.

Vest4

0.29

MutPred

0.58

.;Gain of catalytic residue at L119 (P = 0.0704);Gain of catalytic residue at L119 (P = 0.0704);

MVP

0.31

MPC

0.11

ClinPred

0.32

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.053

gMVP

0.12

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

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