rs2002273

Variant names:

• chr10-49886614-C-T
• rs2002273
• NM_003631.5:c.1738-1319G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PARG	NM_003631.5	c.1738-1319G>A		intron_variant	Intron 7 of 17	ENST00000616448.2	NP_003622.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARG	ENST00000616448.2	c.1738-1319G>A		intron_variant	Intron 7 of 17	1	NM_003631.5	ENSP00000484285.1

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

African (AFR) AF: 0.302 AC: 12482 AN: 41318

American (AMR) AF: 0.207 AC: 3160 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1006 AN: 3468

East Asian (EAS) AF: 0.0916 AC: 473 AN: 5166

South Asian (SAS) AF: 0.253 AC: 1221 AN: 4818

European-Finnish (FIN) AF: 0.352 AC: 3679 AN: 10454

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21670 AN: 67912

Other (OTH) AF: 0.269 AC: 567 AN: 2110

Alfa AF: 0.306 Hom.: 3888

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
PhyloP100		-2.2

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

Other links and lift over

dbSNP: rs2002273; hg19: chr10-51094660;