chr2-201399433-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015049.3(TRAK2):c.424G>A(p.Val142Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 1,610,932 control chromosomes in the GnomAD database, including 347,469 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 25978 hom., cov: 32)

Exomes 𝑓: 0.66 ( 321491 hom. )

Consequence

TRAK2
NM_015049.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.87

Publications

35 publications found

Variant links:

Genes affected

TRAK2 (HGNC:13206): (trafficking kinesin protein 2) Predicted to enable GABA receptor binding activity and myosin binding activity. Predicted to be involved in several processes, including mitochondrion distribution; organelle transport along microtubule; and protein targeting. Predicted to be located in cytoplasm and plasma membrane. Predicted to be active in cytoplasmic vesicle; dendrite; and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

TRAK2 links:

STRADB (HGNC:13205): (STE20 related adaptor beta) This gene encodes a protein that belongs to the serine/threonine protein kinase STE20 subfamily. One of the active site residues in the protein kinase domain of this protein is altered, and it is thus a pseudokinase. This protein is a component of a complex involved in the activation of serine/threonine kinase 11, a master kinase that regulates cell polarity and energy-generating metabolism. This complex regulates the relocation of this kinase from the nucleus to the cytoplasm, and it is essential for G1 cell cycle arrest mediated by this kinase. The protein encoded by this gene can also interact with the X chromosome-linked inhibitor of apoptosis protein, and this interaction enhances the anti-apoptotic activity of this protein via the JNK1 signal transduction pathway. Two pseudogenes, located on chromosomes 1 and 7, have been found for this gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

STRADB links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.022073E-5).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015049.3. 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
	TRAK2	NM_015049.3	MANE Select	c.424G>A	p.Val142Ile	missense	Exon 5 of 16	NP_055864.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TRAK2	ENST00000332624.8	TSL:1 MANE Select	c.424G>A	p.Val142Ile	missense	Exon 5 of 16	ENSP00000328875.3
TRAK2	ENST00000430254.1	TSL:2	c.424G>A	p.Val142Ile	missense	Exon 5 of 8	ENSP00000409333.1
TRAK2	ENST00000486291.1	TSL:3	n.78G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.571

AC:

86618

AN:

151742

Hom.:

25981

Cov.:

show subpopulations

Gnomad AFR

AF:

0.378

Gnomad AMI

AF:

0.459

Gnomad AMR

AF:

0.559

Gnomad ASJ

AF:

0.630

Gnomad EAS

AF:

0.487

Gnomad SAS

AF:

0.686

Gnomad FIN

AF:

0.646

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.676

Gnomad OTH

AF:

0.562

GnomAD2 exomes

AF:

0.621

AC:

155647

AN:

250676

AF XY:

0.633

show subpopulations

Gnomad AFR exome

AF:

0.367

Gnomad AMR exome

AF:

0.554

Gnomad ASJ exome

AF:

0.616

Gnomad EAS exome

AF:

0.502

Gnomad FIN exome

AF:

0.650

Gnomad NFE exome

AF:

0.674

Gnomad OTH exome

AF:

0.624

GnomAD4 exome

AF:

0.660

AC:

962762

AN:

1459072

Hom.:

321491

Cov.:

AF XY:

0.662

AC XY:

480680

AN XY:

725750

show subpopulations

African (AFR)

AF:

0.359

AC:

11972

AN:

33394

American (AMR)

AF:

0.555

AC:

24740

AN:

44614

Ashkenazi Jewish (ASJ)

AF:

0.619

AC:

16125

AN:

26042

East Asian (EAS)

AF:

0.450

AC:

17831

AN:

39626

South Asian (SAS)

AF:

0.688

AC:

59091

AN:

85860

European-Finnish (FIN)

AF:

0.649

AC:

34619

AN:

53342

Middle Eastern (MID)

AF:

0.581

AC:

3343

AN:

5758

European-Non Finnish (NFE)

AF:

0.682

AC:

756756

AN:

1110170

Other (OTH)

AF:

0.635

AC:

38285

AN:

60266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

14765

29530

44296

59061

73826

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19280

38560

57840

77120

96400

<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:

0.570

AC:

86616

AN:

151860

Hom.:

25978

Cov.:

AF XY:

0.570

AC XY:

42319

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.377

AC:

15607

AN:

41410

American (AMR)

AF:

0.559

AC:

8517

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.630

AC:

2186

AN:

3470

East Asian (EAS)

AF:

0.486

AC:

2509

AN:

5162

South Asian (SAS)

AF:

0.685

AC:

3305

AN:

4822

European-Finnish (FIN)

AF:

0.646

AC:

6810

AN:

10538

Middle Eastern (MID)

AF:

0.633

AC:

186

AN:

294

European-Non Finnish (NFE)

AF:

0.676

AC:

45890

AN:

67902

Other (OTH)

AF:

0.565

AC:

1188

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1802

3605

5407

7210

9012

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

742

1484

2226

2968

3710

<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:

0.638

Hom.:

104910

Bravo

AF:

0.549

TwinsUK

AF:

0.683

AC:

2534

ALSPAC

AF:

0.693

AC:

2671

ESP6500AA

AF:

0.374

AC:

1648

ESP6500EA

AF:

0.673

AC:

5787

ExAC

AF:

0.623

AC:

75574

Asia WGS

AF:

0.567

AC:

1973

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.014

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.093

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.64

MetaRNN

Benign

0.000030

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.92

PhyloP100

1.9

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.47

REVEL

Benign

0.046

Sift

Benign

0.45

Sift4G

Benign

0.36

Polyphen

0.0030

Vest4

0.079

MPC

0.098

ClinPred

0.0060

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.027

gMVP

0.094

Mutation Taster

=96/4

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

Computational scores

Splicing

Publications

Other links and lift over