2-201380733-G-C

Variant names:

• chr2-201380733-G-C
• rs1363476975
• NM_015049.3:c.2555C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015049.3(TRAK2):​c.2555C>G​(p.Ala852Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRAK2 NM_015049.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.03

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08886811).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAK2	NM_015049.3	c.2555C>G	p.Ala852Gly	missense_variant	Exon 16 of 16	ENST00000332624.8	NP_055864.2
TRAK2	XM_047445578.1	c.2555C>G	p.Ala852Gly	missense_variant	Exon 16 of 16		XP_047301534.1
TRAK2	XM_047445579.1	c.1922C>G	p.Ala641Gly	missense_variant	Exon 13 of 13		XP_047301535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAK2	ENST00000332624.8	c.2555C>G	p.Ala852Gly	missense_variant	Exon 16 of 16	1	NM_015049.3	ENSP00000328875.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.86
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.079
Sift	Benign	0.16	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.073
MutPred		0.22		Gain of catalytic residue at A852 (P = 0.0102);
MVP		0.095
MPC		0.12
ClinPred		0.12	T
GERP RS		2.9
Varity_R		0.038
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1363476975; hg19: chr2-202245456;