14-20354149-A-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001042618.2(PARP2):c.665A>G(p.Asp222Gly) variant causes a missense change. The variant allele was found at a frequency of 0.02 in 1,612,584 control chromosomes in the GnomAD database, including 470 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.019 ( 49 hom., cov: 32)
Exomes 𝑓: 0.020 ( 421 hom. )
Consequence
PARP2
NM_001042618.2 missense
NM_001042618.2 missense
Scores
1
5
10
Clinical Significance
Conservation
PhyloP100: 7.06
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.003672868).
BP6
?
Variant 14-20354149-A-G is Benign according to our data. Variant chr14-20354149-A-G is described in ClinVar as [Benign]. Clinvar id is 1230992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0186 (2835/152294) while in subpopulation NFE AF= 0.0244 (1659/68026). AF 95% confidence interval is 0.0234. There are 49 homozygotes in gnomad4. There are 1519 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 49 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PARP2 | NM_001042618.2 | c.665A>G | p.Asp222Gly | missense_variant | 8/16 | ENST00000429687.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PARP2 | ENST00000429687.8 | c.665A>G | p.Asp222Gly | missense_variant | 8/16 | 1 | NM_001042618.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0186 AC: 2835AN: 152176Hom.: 49 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0193 AC: 4817AN: 249530Hom.: 98 AF XY: 0.0190 AC XY: 2575AN XY: 135380
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GnomAD4 exome AF: 0.0201 AC: 29389AN: 1460290Hom.: 421 Cov.: 29 AF XY: 0.0195 AC XY: 14203AN XY: 726558
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GnomAD4 genome ? AF: 0.0186 AC: 2835AN: 152294Hom.: 49 Cov.: 32 AF XY: 0.0204 AC XY: 1519AN XY: 74462
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189
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | PARP2: BP4, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 18, 2019 | This variant is associated with the following publications: (PMID: 29484706) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Benign
D;D;D
Sift4G
Benign
T;T;T
Polyphen
B;P;.
Vest4
MPC
0.38
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at