chr14-20345028-A-T

Variant names:

• chr14-20345028-A-T
• rs1244487469
• NM_001042618.2:c.143A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042618.2(PARP2):​c.143A>T​(p.Lys48Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,728 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PARP2 NM_001042618.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

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 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=0.2244277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP2	NM_001042618.2	c.143A>T	p.Lys48Ile	missense_variant	Exon 2 of 16	ENST00000429687.8	NP_001036083.1
PARP2	NM_005484.4	c.143A>T	p.Lys48Ile	missense_variant	Exon 2 of 16		NP_005475.2
PARP2	XM_005267247.4	c.143A>T	p.Lys48Ile	missense_variant	Exon 2 of 15		XP_005267304.1
PARP2	XM_017020912.2	c.143A>T	p.Lys48Ile	missense_variant	Exon 2 of 15		XP_016876401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP2	ENST00000429687.8	c.143A>T	p.Lys48Ile	missense_variant	Exon 2 of 16	1	NM_001042618.2	ENSP00000392972.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249578 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135408

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461728 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727184

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	.;T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.61	T;T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.099
Sift	Uncertain	0.012	D;D;D
Sift4G	Uncertain	0.030	D;D;D
Polyphen		0.79	P;P;.
Vest4		0.29
MutPred		0.23		Loss of catalytic residue at K48 (P = 0.0228);Loss of catalytic residue at K48 (P = 0.0228);Loss of catalytic residue at K48 (P = 0.0228);
MVP		0.54
MPC		0.29
ClinPred		0.39	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.33

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

Other links and lift over

dbSNP: rs1244487469; hg19: chr14-20813187;