chr2-60782678-TAA-T

Variant names:

• chr2-60782678-TAA-T
• rs1449808552
• NM_022894.4:c.1028-7_1028-6delAA

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_022894.4(PAPOLG):​c.1028-7_1028-6delAA variant causes a splice region, 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, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.400

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: Likely_benign. The variant received -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPOLG	NM_022894.4	c.1028-7_1028-6delAA		splice_region_variant, intron_variant	Intron 11 of 21	ENST00000238714.8	NP_075045.2
PAPOLG	XM_005264500.5	c.1028-7_1028-6delAA		splice_region_variant, intron_variant	Intron 11 of 20		XP_005264557.1
PAPOLG	XM_005264501.3	c.896-7_896-6delAA		splice_region_variant, intron_variant	Intron 11 of 21		XP_005264558.1
PAPOLG	XR_007080681.1	n.1239-7_1239-6delAA		splice_region_variant, intron_variant	Intron 11 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPOLG	ENST00000238714.8	c.1028-7_1028-6delAA		splice_region_variant, intron_variant	Intron 11 of 21	1	NM_022894.4	ENSP00000238714.3

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 1799 AN: 124860 Hom.: 0 Cov.: 0

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

GnomAD2 exomes AF: 0.00110 AC: 142 AN: 129158 AF XY: 0.00120

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 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.: 2 AF XY: 0.00189 AC XY: 1173 AN XY: 621950

Gnomad4 AFR exome AF: 0.00109 AC: 26 AN: 23758

Gnomad4 AMR exome AF: 0.00309 AC: 63 AN: 20376

Gnomad4 ASJ exome AF: 0.00342 AC: 62 AN: 18150

Gnomad4 EAS exome AF: 0.00158 AC: 50 AN: 31552

Gnomad4 SAS exome AF: 0.00659 AC: 420 AN: 63706

Gnomad4 FIN exome AF: 0.00762 AC: 326 AN: 42786

Gnomad4 NFE exome AF: 0.00108 AC: 1082 AN: 1003312

Gnomad4 Remaining exome AF: 0.00172 AC: 84 AN: 48912

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0144 AC: 1799 AN: 124910 Hom.: 0 Cov.: 0 AF XY: 0.0137 AC XY: 822 AN XY: 60036

Gnomad4 AFR AF: 0.0140 AC: 0.0140495 AN: 0.0140495

Gnomad4 AMR AF: 0.00645 AC: 0.00644641 AN: 0.00644641

Gnomad4 ASJ AF: 0.0124 AC: 0.0124495 AN: 0.0124495

Gnomad4 EAS AF: 0.00738 AC: 0.0073831 AN: 0.0073831

Gnomad4 SAS AF: 0.00633 AC: 0.0063322 AN: 0.0063322

Gnomad4 FIN AF: 0.0156 AC: 0.0156151 AN: 0.0156151

Gnomad4 NFE AF: 0.0172 AC: 0.0172024 AN: 0.0172024

Gnomad4 OTH AF: 0.0174 AC: 0.0173861 AN: 0.0173861

⚠️ The allele balance in gnomAD4 Genomes is highly skewed (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0531 Hom.: 1

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 14, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs1449808552; hg19: chr2-61009813;