Variant chr2-60782678-TAA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_022894.4(PAPOLG):c.1028-7_1028-6del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,256,392 control chromosomes in the GnomAD database, including 2 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0017 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

PAPOLG
NM_022894.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.400

Variant links:

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]

PAPOLG links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 2-60782678-TAA-T is Benign according to our data. Variant chr2-60782678-TAA-T is described in ClinVar as [Benign]. Clinvar id is 781680.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
PAPOLG	NM_022894.4 linkuse as main transcript	c.1028-7_1028-6del	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000238714.8	NP_075045.2
PAPOLG	XM_005264500.5 linkuse as main transcript	c.1028-7_1028-6del	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		XP_005264557.1
PAPOLG	XM_005264501.3 linkuse as main transcript	c.896-7_896-6del	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		XP_005264558.1
PAPOLG	XR_007080681.1 linkuse as main transcript	n.1239-7_1239-6del	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAPOLG	ENST00000238714.8 linkuse as main transcript	c.1028-7_1028-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_022894.4	ENSP00000238714	P1	Q9BWT3-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1799

AN:

124860

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.0227

Gnomad AMR

AF:

0.00646

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00736

Gnomad SAS

AF:

0.00630

Gnomad FIN

AF:

0.0156

Gnomad MID

AF:

0.00394

Gnomad NFE

AF:

0.0172

Gnomad OTH

AF:

0.0176

GnomAD3 exomes

AF:

0.00110

AC:

142

AN:

129158

Hom.:

AF XY:

0.00120

AC XY:

AN XY:

72432

show subpopulations

Gnomad AFR exome

AF:

0.000733

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00104

Gnomad EAS exome

AF:

0.00264

Gnomad SAS exome

AF:

0.00145

Gnomad FIN exome

AF:

0.00150

Gnomad NFE exome

AF:

0.000675

Gnomad OTH exome

AF:

0.00155

GnomAD4 exome

AF:

0.00169

AC:

2122

AN:

1256392

Hom.:

AF XY:

0.00189

AC XY:

1173

AN XY:

621950

show subpopulations

Gnomad4 AFR exome

AF:

0.00109

Gnomad4 AMR exome

AF:

0.00309

Gnomad4 ASJ exome

AF:

0.00342

Gnomad4 EAS exome

AF:

0.00158

Gnomad4 SAS exome

AF:

0.00659

Gnomad4 FIN exome

AF:

0.00762

Gnomad4 NFE exome

AF:

0.00108

Gnomad4 OTH exome

AF:

0.00172

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0144

AC:

1799

AN:

124910

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

822

AN XY:

60036

show subpopulations

Gnomad4 AFR

AF:

0.0140

Gnomad4 AMR

AF:

0.00645

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.00738

Gnomad4 SAS

AF:

0.00633

Gnomad4 FIN

AF:

0.0156

Gnomad4 NFE

AF:

0.0172

Gnomad4 OTH

AF:

0.0174

Alfa

AF:

0.0531

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 14, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over