2-201381184-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015049.3(TRAK2):​c.2104G>A​(p.Gly702Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,612,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

TRAK2
NM_015049.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.532
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.009349316).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRAK2NM_015049.3 linkuse as main transcriptc.2104G>A p.Gly702Ser missense_variant 16/16 ENST00000332624.8
TRAK2XM_047445578.1 linkuse as main transcriptc.2104G>A p.Gly702Ser missense_variant 16/16
TRAK2XM_047445579.1 linkuse as main transcriptc.1471G>A p.Gly491Ser missense_variant 13/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRAK2ENST00000332624.8 linkuse as main transcriptc.2104G>A p.Gly702Ser missense_variant 16/161 NM_015049.3 P1O60296-1

Frequencies

GnomAD3 genomes
AF:
0.0000530
AC:
8
AN:
150836
Hom.:
0
Cov.:
32
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:
0.000973
Gnomad SAS
AF:
0.000210
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000116
AC:
29
AN:
249074
Hom.:
0
AF XY:
0.0000964
AC XY:
13
AN XY:
134842
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00103
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000625
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000465
AC:
68
AN:
1461188
Hom.:
0
Cov.:
38
AF XY:
0.0000482
AC XY:
35
AN XY:
726788
show subpopulations
Gnomad4 AFR exome
AF:
0.0000897
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00106
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000530
AC:
8
AN:
150952
Hom.:
0
Cov.:
32
AF XY:
0.0000543
AC XY:
4
AN XY:
73664
show subpopulations
Gnomad4 AFR
AF:
0.0000244
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000975
Gnomad4 SAS
AF:
0.000210
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000399
Hom.:
0
ExAC
AF:
0.000107
AC:
13
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000546
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 16, 2023The c.2104G>A (p.G702S) alteration is located in exon 16 (coding exon 15) of the TRAK2 gene. This alteration results from a G to A substitution at nucleotide position 2104, causing the glycine (G) at amino acid position 702 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
15
DANN
Benign
0.53
DEOGEN2
Benign
0.0052
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.28
N
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.0093
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.22
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
0.36
N
REVEL
Benign
0.018
Sift
Benign
0.81
T
Sift4G
Benign
0.75
T
Polyphen
0.0080
B
Vest4
0.20
MVP
0.10
MPC
0.14
ClinPred
0.012
T
GERP RS
1.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.027
gMVP
0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs558396968; hg19: chr2-202245907; COSMIC: COSV60271369; API