2-201389798-T-C

Position:

chr2-201389798-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_015049.3(TRAK2):c.1193+3A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,609,162 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 17 hom., cov: 32)

Exomes 𝑓: 0.012 ( 141 hom. )

Consequence

TRAK2
NM_015049.3 splice_region, intron

Scores

Splicing: ADA: 0.01008

Clinical Significance

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

Conservation

PhyloP100: 0.652

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 2-201389798-T-C is Benign according to our data. Variant chr2-201389798-T-C is described in ClinVar as [Benign]. Clinvar id is 779409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00894 (1362/152324) while in subpopulation NFE AF= 0.0163 (1108/68024). AF 95% confidence interval is 0.0155. There are 17 homozygotes in gnomad4. There are 587 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TRAK2	NM_015049.3 linkuse as main transcript	c.1193+3A>G	splice_region_variant, intron_variant	ENST00000332624.8	NP_055864.2	O60296-1
TRAK2	XM_047445578.1 linkuse as main transcript	c.1193+3A>G	splice_region_variant, intron_variant		XP_047301534.1
TRAK2	XM_047445579.1 linkuse as main transcript	c.560+3A>G	splice_region_variant, intron_variant		XP_047301535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAK2	ENST00000332624.8 linkuse as main transcript	c.1193+3A>G		splice_region_variant, intron_variant		1	NM_015049.3	ENSP00000328875.3		O60296-1
STRADB	ENST00000458269.6 linkuse as main transcript	c.28+1723T>C		intron_variant		5		ENSP00000409552.2		C9JSU7

Frequencies

GnomAD3 genomes

AF:

0.00895

AC:

1363

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00244

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00443

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0163

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00805

AC:

2002

AN:

248772

Hom.:

AF XY:

0.00788

AC XY:

1060

AN XY:

134440

show subpopulations

Gnomad AFR exome

AF:

0.00228

Gnomad AMR exome

AF:

0.00339

Gnomad ASJ exome

AF:

0.000400

Gnomad EAS exome

AF:

0.00252

Gnomad SAS exome

AF:

0.000670

Gnomad FIN exome

AF:

0.00519

Gnomad NFE exome

AF:

0.0142

Gnomad OTH exome

AF:

0.0100

GnomAD4 exome

AF:

0.0121

AC:

17658

AN:

1456838

Hom.:

141

Cov.:

AF XY:

0.0118

AC XY:

8519

AN XY:

724948

show subpopulations

Gnomad4 AFR exome

AF:

0.00178

Gnomad4 AMR exome

AF:

0.00343

Gnomad4 ASJ exome

AF:

0.000269

Gnomad4 EAS exome

AF:

0.00182

Gnomad4 SAS exome

AF:

0.000748

Gnomad4 FIN exome

AF:

0.00589

Gnomad4 NFE exome

AF:

0.0148

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.00894

AC:

1362

AN:

152324

Hom.:

Cov.:

AF XY:

0.00788

AC XY:

587

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00243

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00443

Gnomad4 NFE

AF:

0.0163

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.00839

Asia WGS

AF:

0.00116

AC:

AN:

3474

EpiCase

AF:

0.0118

EpiControl

AF:

0.0112

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.010

dbscSNV1_RF

Benign

0.10

SpliceAI score (max)

0.020

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