rs28459296

Variant names:

• chr2-60767303-A-G
• rs28459296
• NM_022894.4:c.247-1167A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-60767303-A-G
• chr2-60767303-A-T

Variant summary

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

The NM_022894.4(PAPOLG):​c.247-1167A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 151,608 control chromosomes in the GnomAD database, including 5,482 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 0.26 (5482 hom., cov: 31)
• Consequence: PAPOLG NM_022894.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 8 publications found

Genes affected

PAPOLG (HGNC:14982): (poly(A) polymerase gamma) This gene encodes a member of the poly(A) polymerase family which catalyzes template-independent extension of the 3' end of a DNA/RNA strand. This enzyme shares 60% identity to the well characterized poly(A) polymerase II (PAPII) at the amino acid level. These two enzymes have similar organization of structural and functional domains. This enzyme is exclusively localized in the nucleus and exhibits both nonspecific and CPSF (cleavage and polyadenylation specificity factor)/AAUAAA-dependent polyadenylation activity. This gene is located on chromosome 2 in contrast to the PAPII gene, which is located on chromosome 14. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPOLG	NM_022894.4	c.247-1167A>G		intron_variant	Intron 3 of 21	ENST00000238714.8	NP_075045.2
PAPOLG	XM_005264500.5	c.247-1167A>G		intron_variant	Intron 3 of 20		XP_005264557.1
PAPOLG	XM_005264501.3	c.115-1167A>G		intron_variant	Intron 3 of 21		XP_005264558.1
PAPOLG	XR_007080681.1	n.458-1167A>G		intron_variant	Intron 3 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPOLG	ENST00000238714.8	c.247-1167A>G		intron_variant	Intron 3 of 21	1	NM_022894.4	ENSP00000238714.3
PAPOLG	ENST00000414060.5	n.115-1167A>G		intron_variant	Intron 3 of 20	1		ENSP00000405599.1
PAPOLG	ENST00000453839.5	n.229-1167A>G		intron_variant	Intron 2 of 19	1		ENSP00000414070.1
PAPOLG	ENST00000496283.5	n.327-1167A>G		intron_variant	Intron 3 of 18	1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39742 AN: 151510 Hom.: 5473 Cov.: 31

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.262 AC: 39774 AN: 151608 Hom.: 5482 Cov.: 31 AF XY: 0.265 AC XY: 19603 AN XY: 74054

African (AFR) AF: 0.230 AC: 9497 AN: 41338

American (AMR) AF: 0.240 AC: 3659 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 941 AN: 3470

East Asian (EAS) AF: 0.108 AC: 557 AN: 5178

South Asian (SAS) AF: 0.180 AC: 860 AN: 4784

European-Finnish (FIN) AF: 0.368 AC: 3822 AN: 10398

Middle Eastern (MID) AF: 0.351 AC: 101 AN: 288

European-Non Finnish (NFE) AF: 0.289 AC: 19625 AN: 67882

Other (OTH) AF: 0.261 AC: 549 AN: 2106

Alfa AF: 0.282 Hom.: 1575

Bravo AF: 0.250

Asia WGS AF: 0.138 AC: 480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs28459296; hg19: chr2-60994438;