chr14-20345100-G-A

Variant names:

• chr14-20345100-G-A
• ENST00000250416.9:c.215G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005484.4(PARP2):​c.215G>A​(p.Arg72Lys) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PARP2 NM_005484.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44

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]

ENSG00000254846 (HGNC:):

ACMG classification

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=0.06168005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP2	NM_001042618.2	c.202+13G>A		intron_variant	Intron 2 of 15	ENST00000429687.8	NP_001036083.1
PARP2	NM_005484.4	c.215G>A	p.Arg72Lys	missense_variant	Exon 2 of 16		NP_005475.2
PARP2	XM_005267247.4	c.215G>A	p.Arg72Lys	missense_variant	Exon 2 of 15		XP_005267304.1
PARP2	XM_017020912.2	c.202+13G>A		intron_variant	Intron 2 of 14		XP_016876401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP2	ENST00000429687.8	c.202+13G>A		intron_variant	Intron 2 of 15	1	NM_001042618.2	ENSP00000392972.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.215G>A (p.R72K) alteration is located in exon 2 (coding exon 2) of the PARP2 gene. This alteration results from a G to A substitution at nucleotide position 215, causing the arginine (R) at amino acid position 72 to be replaced by a lysine (K). 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	0.068
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.3
DANN	Benign	0.60
DEOGEN2	Benign	0.015	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.23	T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.062	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.49	N;N
REVEL	Benign	0.036
Sift	Benign	0.95	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.20
MutPred		0.29		Gain of ubiquitination at R72 (P = 0.0051);Gain of ubiquitination at R72 (P = 0.0051);
MVP		0.35
MPC		0.10
ClinPred		0.046	T
GERP RS		-0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.042
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-20813259;