dbSNP rs558396968: TRAK2:p.Gly702Cys (chr2-201381184-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015049.3(TRAK2):c.2104G>T(p.Gly702Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000663 in 150,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G702S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

TRAK2
NM_015049.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.532

Publications

2 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17145088).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAK2	NM_015049.3	MANE Select	c.2104G>T	p.Gly702Cys	missense	Exon 16 of 16	NP_055864.2	O60296-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRAK2	ENST00000332624.8	TSL:1 MANE Select	c.2104G>T	p.Gly702Cys	missense	Exon 16 of 16	ENSP00000328875.3	O60296-1
TRAK2	ENST00000861749.1		c.2173G>T	p.Gly725Cys	missense	Exon 17 of 17	ENSP00000531808.1
TRAK2	ENST00000861746.1		c.2104G>T	p.Gly702Cys	missense	Exon 16 of 16	ENSP00000531805.1

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150834

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150834

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73536

show subpopulations

African (AFR)

AF:

0.0000245

AC:

AN:

40858

American (AMR)

AF:

0.00

AC:

AN:

15094

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67898

Other (OTH)

AF:

0.00

AC:

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0076

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.64

M_CAP

Benign

0.019

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

0.53

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.3

REVEL

Benign

0.082

Sift

Benign

0.060

Sift4G

Uncertain

0.053

Polyphen

0.97

Vest4

0.32

MutPred

0.18

Loss of relative solvent accessibility (P = 0.0306)

MVP

0.38

MPC

0.18

ClinPred

0.40

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.096

gMVP

0.33

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over