rs28459296

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PAPOLG	NM_022894.4	c.247-1167A>G		intron_variant		ENST00000238714.8
PAPOLG	XM_005264500.5	c.247-1167A>G		intron_variant
PAPOLG	XM_005264501.3	c.115-1167A>G		intron_variant
PAPOLG	XR_007080681.1	n.458-1167A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAPOLG	ENST00000238714.8	c.247-1167A>G		intron_variant		1	NM_022894.4	P1
PAPOLG	ENST00000414060.5	c.115-1167A>G		intron_variant, NMD_transcript_variant		1
PAPOLG	ENST00000453839.5	c.229-1167A>G		intron_variant, NMD_transcript_variant		1
PAPOLG	ENST00000496283.5	n.327-1167A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.261

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs28459296; hg19: chr2-60994438;