Variant 14-20345124-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000429687.8(PARP2):c.202+37C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PARP2
ENST00000429687.8 intron

Scores

Splicing: ADA: 0.001590

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.23

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0856604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PARP2	NM_001042618.2 linkuse as main transcript	c.202+37C>G		intron_variant		ENST00000429687.8	NP_001036083.1
PARP2	NM_005484.4 linkuse as main transcript	c.239C>G	p.Ser80Cys	missense_variant, splice_region_variant	2/16		NP_005475.2
PARP2	XM_005267247.4 linkuse as main transcript	c.239C>G	p.Ser80Cys	missense_variant, splice_region_variant	2/15		XP_005267304.1
PARP2	XM_017020912.2 linkuse as main transcript	c.202+37C>G		intron_variant			XP_016876401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP2	ENST00000429687.8 linkuse as main transcript	c.202+37C>G		intron_variant		1	NM_001042618.2	ENSP00000392972	P2	Q9UGN5-2
	ENST00000528210.1 linkuse as main transcript	n.325-748G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248630

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00

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:

1457912

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725282

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

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

Jan 09, 2024

The c.239C>G (p.S80C) alteration is located in exon 2 (coding exon 2) of the PARP2 gene. This alteration results from a C to G substitution at nucleotide position 239, causing the serine (S) at amino acid position 80 to be replaced by a cysteine (C). 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

0.084

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.3

DANN

Benign

0.65

DEOGEN2

Benign

0.084

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.22

T;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.086

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.0070

Sift

Benign

0.061

T;T

Sift4G

Benign

0.064

T;T

Polyphen

0.0

B;.

Vest4

0.10

MutPred

0.41

Loss of phosphorylation at S80 (P = 0.013);Loss of phosphorylation at S80 (P = 0.013);

MVP

0.22

MPC

0.097

ClinPred

0.12

GERP RS

-6.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.070

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0016

dbscSNV1_RF

Benign

0.12

SpliceAI score (max)

0.42

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.21

Position offset: -5

DS_DL_spliceai

0.42

Position offset: 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