15-89326537-AC-ACC

Variant names:

Variant summary

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

The NM_002693.3(POLG):c.1712+74dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,546,892 control chromosomes in the GnomAD database, including 85,876 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6483 hom., cov: 23)

Exomes 𝑓: 0.33 ( 79393 hom. )

Consequence

POLG
NM_002693.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.262

Publications

7 publications found

Variant links:

Genes affected

POLG (HGNC:9179): (DNA polymerase gamma, catalytic subunit) Mitochondrial DNA polymerase is heterotrimeric, consisting of a homodimer of accessory subunits plus a catalytic subunit. The protein encoded by this gene is the catalytic subunit of mitochondrial DNA polymerase. The encoded protein contains a polyglutamine tract near its N-terminus that may be polymorphic. Defects in this gene are a cause of progressive external ophthalmoplegia with mitochondrial DNA deletions 1 (PEOA1), sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO), Alpers-Huttenlocher syndrome (AHS), and mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE). Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

POLG links:

MIR6766 (HGNC:49941): (microRNA 6766) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6766 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 15-89326537-A-AC is Benign according to our data. Variant chr15-89326537-A-AC is described in ClinVar as [Benign]. Clinvar id is 1251136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLG	NM_002693.3 link	c.1712+74dupG		intron_variant	Intron 9 of 22	ENST00000268124.11	NP_002684.1	P54098E5KNU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLG	ENST00000268124.11 link	c.1712+74_1712+75insG		intron_variant	Intron 9 of 22	1	NM_002693.3	ENSP00000268124.5		P54098

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40777

AN:

151944

Hom.:

6482

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0907

Gnomad AMI

AF:

0.347

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.372

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.342

Gnomad OTH

AF:

0.281

GnomAD4 exome

AF:

0.334

AC:

465250

AN:

1394830

Hom.:

79393

AF XY:

0.336

AC XY:

233057

AN XY:

694464

show subpopulations

African (AFR)

AF:

0.0771

AC:

2501

AN:

32452

American (AMR)

AF:

0.333

AC:

14601

AN:

43900

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

9441

AN:

25210

East Asian (EAS)

AF:

0.284

AC:

11107

AN:

39148

South Asian (SAS)

AF:

0.378

AC:

32074

AN:

84816

European-Finnish (FIN)

AF:

0.337

AC:

15006

AN:

44480

Middle Eastern (MID)

AF:

0.313

AC:

1660

AN:

5306

European-Non Finnish (NFE)

AF:

0.339

AC:

360094

AN:

1061428

Other (OTH)

AF:

0.323

AC:

18766

AN:

58090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

15277

30555

45832

61110

76387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.268

AC:

40775

AN:

152062

Hom.:

6483

Cov.:

AF XY:

0.274

AC XY:

20372

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.0905

AC:

3758

AN:

41518

American (AMR)

AF:

0.300

AC:

4589

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.372

AC:

1290

AN:

3466

East Asian (EAS)

AF:

0.306

AC:

1579

AN:

5156

South Asian (SAS)

AF:

0.373

AC:

1801

AN:

4828

European-Finnish (FIN)

AF:

0.337

AC:

3560

AN:

10550

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.342

AC:

23207

AN:

67948

Other (OTH)

AF:

0.278

AC:

588

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1466

2932

4397

5863

7329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.142

Hom.:

328

Bravo

AF:

0.258

Asia WGS

AF:

0.309

AC:

1072

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 35% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 33. Only high quality variants are reported. -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.26

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.

15-89326537-AC-ACC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over