17-64482911-TA-TAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_007215.4(POLG2):c.1191+7dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,474,986 control chromosomes in the GnomAD database, including 21,512 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 8817 hom., cov: 26)

Exomes 𝑓: 0.10 ( 12695 hom. )

Consequence

POLG2
NM_007215.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.61

Publications

0 publications found

Variant links:

Genes affected

POLG2 (HGNC:9180): (DNA polymerase gamma 2, accessory subunit) This gene encodes the processivity subunit of the mitochondrial DNA polymerase gamma. The encoded protein forms a heterotrimer containing one catalytic subunit and two processivity subunits. This protein enhances DNA binding and promotes processive DNA synthesis. Mutations in this gene result in autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions.[provided by RefSeq, Sep 2009]

POLG2 links:

MILR1 (HGNC:27570): (mast cell immunoglobulin like receptor 1) Predicted to enable transmembrane signaling receptor activity. Predicted to be involved in several processes, including cell-cell adhesion via plasma-membrane adhesion molecules; mast cell degranulation; and negative regulation of mast cell activation. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

MILR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 17-64482911-T-TA is Benign according to our data. Variant chr17-64482911-T-TA is described in ClinVar as Benign. ClinVar VariationId is 260154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007215.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLG2	NM_007215.4	MANE Select	c.1191+7dupT		splice_region intron	N/A	NP_009146.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
POLG2	ENST00000539111.7	TSL:1 MANE Select	c.1191+7_1191+8insT	splice_region intron	N/A	ENSP00000442563.2
MILR1	ENST00000718368.1		c.29-9374_29-9373insA	intron	N/A	ENSP00000520798.1
POLG2	ENST00000581355.1	TSL:3	c.450+7_450+8insT	splice_region intron	N/A	ENSP00000462071.1

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38412

AN:

151994

Hom.:

8791

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.0855

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.0340

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0966

Gnomad OTH

AF:

0.205

GnomAD2 exomes

AF:

0.144

AC:

36179

AN:

251140

AF XY:

0.132

show subpopulations

Gnomad AFR exome

AF:

0.634

Gnomad AMR exome

AF:

0.201

Gnomad ASJ exome

AF:

0.0998

Gnomad EAS exome

AF:

0.0314

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.0938

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.105

AC:

138624

AN:

1322874

Hom.:

12695

Cov.:

AF XY:

0.104

AC XY:

69197

AN XY:

665890

show subpopulations

African (AFR)

AF:

0.628

AC:

18717

AN:

29806

American (AMR)

AF:

0.204

AC:

9075

AN:

44498

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

2521

AN:

25212

East Asian (EAS)

AF:

0.0354

AC:

1382

AN:

39054

South Asian (SAS)

AF:

0.117

AC:

9721

AN:

83414

European-Finnish (FIN)

AF:

0.116

AC:

6191

AN:

53340

Middle Eastern (MID)

AF:

0.120

AC:

661

AN:

5518

European-Non Finnish (NFE)

AF:

0.0848

AC:

83668

AN:

986318

Other (OTH)

AF:

0.120

AC:

6688

AN:

55714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

5046

10092

15139

20185

25231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3014

6028

9042

12056

15070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.253

AC:

38485

AN:

152112

Hom.:

8817

Cov.:

AF XY:

0.251

AC XY:

18641

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.615

AC:

25502

AN:

41444

American (AMR)

AF:

0.236

AC:

3609

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

351

AN:

3470

East Asian (EAS)

AF:

0.0339

AC:

176

AN:

5192

South Asian (SAS)

AF:

0.108

AC:

523

AN:

4826

European-Finnish (FIN)

AF:

0.115

AC:

1214

AN:

10596

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0966

AC:

6571

AN:

67996

Other (OTH)

AF:

0.203

AC:

427

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1049

2098

3148

4197

5246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.158

Hom.:

781

Bravo

AF:

0.275

Asia WGS

AF:

0.103

AC:

359

AN:

3478

EpiCase

AF:

0.0949

EpiControl

AF:

0.0977

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 22, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Progressive external ophthalmoplegia with mitochondrial DNA deletions

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mitochondrial dna depletion syndrome 16B (neuroophthalmic type)

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mitochondrial DNA depletion syndrome 16 (hepatic type)

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4;C5193142:Mitochondrial DNA depletion syndrome 16 (hepatic type);C5543632:Mitochondrial dna depletion syndrome 16B (neuroophthalmic type)

Benign:1

Aug 06, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over