2-201381221-TAAAAA-TAAA

Variant names:

• chr2-201381221-TAA-T
• rs3832088
• NM_015049.3:c.2070-5_2070-4delTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_015049.3(TRAK2):​c.2070-5_2070-4delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 1,511,968 control chromosomes in the GnomAD database, including 339,181 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (25936 hom., cov: 0)
  • Exomes 𝑓: 0.68 (313245 hom.)
• Consequence: TRAK2 NM_015049.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.686 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAK2	NM_015049.3	MANE Select	c.2070-5_2070-4delTT		splice_region intron	N/A	NP_055864.2	O60296-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAK2	ENST00000332624.8	TSL:1 MANE Select	c.2070-5_2070-4delTT		splice_region intron	N/A	ENSP00000328875.3	O60296-1
	TRAK2	ENST00000861749.1		c.2139-5_2139-4delTT		splice_region intron	N/A	ENSP00000531808.1
	TRAK2	ENST00000861746.1		c.2070-5_2070-4delTT		splice_region intron	N/A	ENSP00000531805.1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 86263 AN: 144792 Hom.: 25940 Cov.: 0

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.586

GnomAD2 exomes AF: 0.704 AC: 124570 AN: 176994 AF XY: 0.713

Gnomad AFR exome AF: 0.462

Gnomad AMR exome AF: 0.654

Gnomad ASJ exome AF: 0.711

Gnomad EAS exome AF: 0.591

Gnomad FIN exome AF: 0.726

Gnomad NFE exome AF: 0.740

Gnomad OTH exome AF: 0.707

GnomAD4 exome AF: 0.678 AC: 926296 AN: 1367130 Hom.: 313245 AF XY: 0.681 AC XY: 458852 AN XY: 674052

African (AFR) AF: 0.380 AC: 10917 AN: 28738

American (AMR) AF: 0.609 AC: 18619 AN: 30550

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 14636 AN: 22556

East Asian (EAS) AF: 0.468 AC: 17428 AN: 37238

South Asian (SAS) AF: 0.729 AC: 54626 AN: 74930

European-Finnish (FIN) AF: 0.681 AC: 33889 AN: 49780

Middle Eastern (MID) AF: 0.605 AC: 3157 AN: 5222

European-Non Finnish (NFE) AF: 0.693 AC: 736442 AN: 1062180

Other (OTH) AF: 0.654 AC: 36582 AN: 55936

GnomAD4 genome AF: 0.596 AC: 86258 AN: 144838 Hom.: 25936 Cov.: 0 AF XY: 0.598 AC XY: 42137 AN XY: 70500

African (AFR) AF: 0.412 AC: 15545 AN: 37730

American (AMR) AF: 0.582 AC: 8480 AN: 14576

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2179 AN: 3408

East Asian (EAS) AF: 0.507 AC: 2477 AN: 4888

South Asian (SAS) AF: 0.706 AC: 3319 AN: 4698

European-Finnish (FIN) AF: 0.688 AC: 6766 AN: 9836

Middle Eastern (MID) AF: 0.665 AC: 185 AN: 278

European-Non Finnish (NFE) AF: 0.687 AC: 45711 AN: 66550

Other (OTH) AF: 0.588 AC: 1185 AN: 2014

Alfa AF: 0.468 Hom.: 1046

Bravo AF: 0.550

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs3832088; hg19: chr2-202245944;