rs11687951

Positions:

• chr2-60776192-G-C
• chr2-60776192-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAPOLG	NM_022894.4	c.694+1069G>C		intron_variant		ENST00000238714.8	NP_075045.2
PAPOLG	XM_005264500.5	c.694+1069G>C		intron_variant			XP_005264557.1
PAPOLG	XM_005264501.3	c.562+1069G>C		intron_variant			XP_005264558.1
PAPOLG	XR_007080681.1	n.905+1069G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAPOLG	ENST00000238714.8	c.694+1069G>C		intron_variant		1	NM_022894.4	ENSP00000238714	P1
PAPOLG	ENST00000414060.5	c.562+1069G>C		intron_variant, NMD_transcript_variant		1		ENSP00000405599
PAPOLG	ENST00000453839.5	c.*57+1069G>C		intron_variant, NMD_transcript_variant		1		ENSP00000414070
PAPOLG	ENST00000496283.5	n.662+1069G>C		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.250

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.67

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: rs11687951; hg19: chr2-61003327;