Variant chr16-66509054-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004614.5(TK2):c.*2914C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0606 in 152,392 control chromosomes in the GnomAD database, including 387 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 387 hom., cov: 33)

Exomes 𝑓: 0.027 ( 0 hom. )

Consequence

TK2
NM_004614.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.797

Variant links:

Genes affected

TK2 (HGNC:11831): (thymidine kinase 2) This gene encodes a deoxyribonucleoside kinase that specifically phosphorylates thymidine, deoxycytidine, and deoxyuridine. The encoded enzyme localizes to the mitochondria and is required for mitochondrial DNA synthesis. Mutations in this gene are associated with a myopathic form of mitochondrial DNA depletion syndrome. Alternate splicing results in multiple transcript variants encoding distinct isoforms, some of which lack transit peptide, so are not localized to mitochondria. [provided by RefSeq, Dec 2012]

TK2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 16-66509054-G-A is Benign according to our data. Variant chr16-66509054-G-A is described in ClinVar as [Benign]. Clinvar id is 320121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TK2	NM_004614.5 linkuse as main transcript	c.*2914C>T		3_prime_UTR_variant	10/10	ENST00000544898.6	NP_004605.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TK2	ENST00000544898.6 linkuse as main transcript	c.*2914C>T		3_prime_UTR_variant	10/10	1	NM_004614.5	ENSP00000440898	P1	O00142-1

Frequencies

GnomAD3 genomes

AF:

0.0606

AC:

9222

AN:

152128

Hom.:

387

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0769

Gnomad AMI

AF:

0.0407

Gnomad AMR

AF:

0.0704

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.160

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.0509

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0364

Gnomad OTH

AF:

0.0599

GnomAD4 exome

AF:

0.0274

AC:

AN:

146

Hom.:

Cov.:

AF XY:

0.0213

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.00909

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0606

AC:

9232

AN:

152246

Hom.:

387

Cov.:

AF XY:

0.0642

AC XY:

4776

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0770

Gnomad4 AMR

AF:

0.0704

Gnomad4 ASJ

AF:

0.0216

Gnomad4 EAS

AF:

0.160

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.0509

Gnomad4 NFE

AF:

0.0364

Gnomad4 OTH

AF:

0.0602

Alfa

AF:

0.0396

Hom.:

141

Bravo

AF:

0.0612

Asia WGS

AF:

0.147

AC:

510

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mitochondrial DNA depletion syndrome, myopathic form

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.41

DANN

Benign

0.44

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