2-60776192-G-C

Variant names:

• chr2-60776192-G-C
• rs11687951
• NM_022894.4:c.694+1069G>C

Variant summary

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

The NM_022894.4(PAPOLG):​c.694+1069G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,096 control chromosomes in the GnomAD database, including 5,033 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 0.25 (5033 hom., cov: 32)
• Consequence: PAPOLG NM_022894.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022894.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAPOLG	NM_022894.4	MANE Select	c.694+1069G>C		intron	N/A	NP_075045.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAPOLG	ENST00000238714.8	TSL:1 MANE Select	c.694+1069G>C		intron	N/A	ENSP00000238714.3	Q9BWT3-1
	PAPOLG	ENST00000414060.5	TSL:1	n.562+1069G>C		intron	N/A	ENSP00000405599.1	F8WAT4
	PAPOLG	ENST00000453839.5	TSL:1	n.*57+1069G>C		intron	N/A	ENSP00000414070.1	H7C3W0

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37709 AN: 151978 Hom.: 5031 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.248 AC: 37724 AN: 152096 Hom.: 5033 Cov.: 32 AF XY: 0.251 AC XY: 18644 AN XY: 74348

African (AFR) AF: 0.183 AC: 7615 AN: 41504

American (AMR) AF: 0.234 AC: 3579 AN: 15274

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

East Asian (EAS) AF: 0.109 AC: 563 AN: 5186

South Asian (SAS) AF: 0.178 AC: 861 AN: 4828

European-Finnish (FIN) AF: 0.361 AC: 3807 AN: 10534

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19565 AN: 67980

Other (OTH) AF: 0.250 AC: 529 AN: 2114

Alfa AF: 0.289 Hom.: 840

Bravo AF: 0.235

Asia WGS AF: 0.135 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.67
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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: rs11687951; hg19: chr2-61003327;