chr2-201387893-G-A

Position:

• chr2-201387893-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_015049.3(TRAK2):​c.1506C>T​(p.Phe502=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00171 in 1,614,148 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0093 (16 hom., cov: 32)
  • Exomes 𝑓: 0.00092 (19 hom.)
• Consequence: TRAK2 NM_015049.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.90

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]

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 2-201387893-G-A is Benign according to our data. Variant chr2-201387893-G-A is described in ClinVar as [Benign]. Clinvar id is 767841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00931 (1417/152260) while in subpopulation AFR AF= 0.0327 (1358/41542). AF 95% confidence interval is 0.0312. There are 16 homozygotes in gnomad4. There are 650 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAK2	NM_015049.3	c.1506C>T	p.Phe502=	synonymous_variant	13/16	ENST00000332624.8
TRAK2	XM_047445578.1	c.1506C>T	p.Phe502=	synonymous_variant	13/16
TRAK2	XM_047445579.1	c.873C>T	p.Phe291=	synonymous_variant	10/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAK2	ENST00000332624.8	c.1506C>T	p.Phe502=	synonymous_variant	13/16	1	NM_015049.3	P1
STRADB	ENST00000458269.6	c.-155G>A		5_prime_UTR_variant	1/6	5

Frequencies

GnomAD3 genomes AF: 0.00933 AC: 1419 AN: 152142 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00622

GnomAD3 exomes AF: 0.00230 AC: 578 AN: 251046 Hom.: 10 AF XY: 0.00151 AC XY: 205 AN XY: 135662

Gnomad AFR exome AF: 0.0315

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000923 AC: 1349 AN: 1461888 Hom.: 19 Cov.: 33 AF XY: 0.000776 AC XY: 564 AN XY: 727242

Gnomad4 AFR exome AF: 0.0333

Gnomad4 AMR exome AF: 0.00168

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000189

Gnomad4 OTH exome AF: 0.00224

GnomAD4 genome AF: 0.00931 AC: 1417 AN: 152260 Hom.: 16 Cov.: 32 AF XY: 0.00873 AC XY: 650 AN XY: 74452

Gnomad4 AFR AF: 0.0327

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00304 Hom.: 5

Bravo AF: 0.0103

Asia WGS AF: 0.00115 AC: 4 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	13
DANN	Benign	0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs116586259; hg19: chr2-202252616;