14-20358084-A-C

Variant names:

• chr14-20358084-A-C
• rs3093942
• NM_001042618.2:c.*287A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042618.2(PARP2):​c.*287A>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,072 control chromosomes in the GnomAD database, including 2,889 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2889 hom., cov: 32)
• Consequence: PARP2 NM_001042618.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 13 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP2	NM_001042618.2	c.*287A>C		downstream_gene_variant		ENST00000429687.8	NP_001036083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP2	ENST00000429687.8	c.*287A>C		downstream_gene_variant		1	NM_001042618.2	ENSP00000392972.3
PARP2	ENST00000250416.9	c.*287A>C		downstream_gene_variant		1		ENSP00000250416.5
PARP2	ENST00000527915.5	c.*560A>C		downstream_gene_variant		2		ENSP00000432283.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27754 AN: 151954 Hom.: 2893 Cov.: 32

Gnomad AFR AF: 0.0866

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.182

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.183 AC: 27755 AN: 152072 Hom.: 2889 Cov.: 32 AF XY: 0.182 AC XY: 13493 AN XY: 74318

African (AFR) AF: 0.0864 AC: 3586 AN: 41500

American (AMR) AF: 0.183 AC: 2792 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3468

East Asian (EAS) AF: 0.279 AC: 1442 AN: 5160

South Asian (SAS) AF: 0.292 AC: 1404 AN: 4810

European-Finnish (FIN) AF: 0.226 AC: 2383 AN: 10554

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14905 AN: 67978

Other (OTH) AF: 0.184 AC: 389 AN: 2112

Alfa AF: 0.217 Hom.: 2993

Bravo AF: 0.174

Asia WGS AF: 0.277 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.6
DANN	Benign	0.72
PhyloP100		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3093942; hg19: chr14-20826243;