rs2002273

Positions:

• chr10-49886614-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003631.5(PARG):​c.1738-1319G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,702 control chromosomes in the GnomAD database, including 6,687 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 0.29 (6687 hom., cov: 32)
• Consequence: PARG NM_003631.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16

Genes affected

PARG (HGNC:8605): (poly(ADP-ribose) glycohydrolase) Poly(ADP-ribose) glycohydrolase (PARG) is the major enzyme responsible for the catabolism of poly(ADP-ribose), a reversible covalent-modifier of chromosomal proteins. The protein is found in many tissues and may be subject to proteolysis generating smaller, active products. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARG	NM_003631.5	c.1738-1319G>A		intron_variant		ENST00000616448.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARG	ENST00000616448.2	c.1738-1319G>A		intron_variant		1	NM_003631.5	P1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44544 AN: 151586 Hom.: 6665 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.0919

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.294 AC: 44613 AN: 151702 Hom.: 6687 Cov.: 32 AF XY: 0.292 AC XY: 21636 AN XY: 74122

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.0916

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.269

Alfa AF: 0.313 Hom.: 2496

Bravo AF: 0.279

Asia WGS AF: 0.176 AC: 609 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.086
DANN	Benign	0.26

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: rs2002273; hg19: chr10-51094660;