17-64482911-TA-TAA

Variant names:

• chr17-64482911-T-TA
• rs60611997
• NM_007215.4:c.1191+7dupT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 2.61
• Publications: 0 publications found

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]

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]

ACMG classification

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

Sel.	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	E5KS15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLG2	ENST00000539111.7	TSL:1 MANE Select	c.1191+7_1191+8insT		splice_region intron	N/A	ENSP00000442563.2	Q9UHN1
	POLG2	ENST00000913014.1		c.1215+7_1215+8insT		splice_region intron	N/A	ENSP00000583073.1
	POLG2	ENST00000913015.1		c.1135-2523_1135-2522insT		intron	N/A	ENSP00000583074.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38412 AN: 151994 Hom.: 8791 Cov.: 26

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

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.: 20 AF XY: 0.104 AC XY: 69197 AN XY: 665890

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

GnomAD4 genome AF: 0.253 AC: 38485 AN: 152112 Hom.: 8817 Cov.: 26 AF XY: 0.251 AC XY: 18641 AN XY: 74368

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: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0966 AC: 6571 AN: 67996

Other (OTH) AF: 0.203 AC: 427 AN: 2104

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Mitochondrial DNA depletion syndrome 16 (hepatic type) (1)
-	-	1	Mitochondrial dna depletion syndrome 16B (neuroophthalmic type) (1)
-	-	1	not specified (1)
-	-	1	Progressive external ophthalmoplegia with mitochondrial DNA deletions (1)
-	-	1	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 (1)
-	-	1	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) (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs60611997; hg19: chr17-62479028;