14-20346864-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001042618.2(PARP2):​c.275C>G​(p.Ala92Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000113 in 1,599,042 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

PARP2
NM_001042618.2 missense, splice_region

Scores

2
5
12
Splicing: ADA: 0.9905
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.61
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PARP2NM_001042618.2 linkc.275C>G p.Ala92Gly missense_variant, splice_region_variant Exon 4 of 16 ENST00000429687.8 NP_001036083.1 Q9UGN5-2
PARP2NM_005484.4 linkc.314C>G p.Ala105Gly missense_variant, splice_region_variant Exon 4 of 16 NP_005475.2 Q9UGN5-1
PARP2XM_005267247.4 linkc.314C>G p.Ala105Gly missense_variant, splice_region_variant Exon 4 of 15 XP_005267304.1
PARP2XM_017020912.2 linkc.275C>G p.Ala92Gly missense_variant, splice_region_variant Exon 4 of 15 XP_016876401.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PARP2ENST00000429687.8 linkc.275C>G p.Ala92Gly missense_variant, splice_region_variant Exon 4 of 16 1 NM_001042618.2 ENSP00000392972.3 Q9UGN5-2

Frequencies

GnomAD3 genomes
AF:
0.0000198
AC:
3
AN:
151826
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000726
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000201
AC:
5
AN:
248356
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
134910
show subpopulations
Gnomad AFR exome
AF:
0.000258
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000104
AC:
15
AN:
1447216
Hom.:
0
Cov.:
28
AF XY:
0.0000111
AC XY:
8
AN XY:
720998
show subpopulations
Gnomad4 AFR exome
AF:
0.000121
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:
0.00000999
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000198
AC:
3
AN:
151826
Hom.:
0
Cov.:
30
AF XY:
0.0000135
AC XY:
1
AN XY:
74122
show subpopulations
Gnomad4 AFR
AF:
0.0000726
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000793
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000533
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000248
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 14, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.314C>G (p.A105G) alteration is located in exon 4 (coding exon 4) of the PARP2 gene. This alteration results from a C to G substitution at nucleotide position 314, causing the alanine (A) at amino acid position 105 to be replaced by a glycine (G). 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
0.22
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.25
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.32
.;T;.
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Benign
0.0042
T
MetaRNN
Uncertain
0.49
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
.;L;.
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-2.2
N;N;N
REVEL
Benign
0.21
Sift
Benign
0.28
T;T;T
Sift4G
Benign
0.31
T;T;T
Polyphen
0.99
D;D;.
Vest4
0.64
MVP
0.63
MPC
0.12
ClinPred
0.21
T
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.39
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
0.99
dbscSNV1_RF
Pathogenic
0.83
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.

Other links and lift over

dbSNP: rs369388288; hg19: chr14-20815023; API