rs2062008409

Variant names:

• chr20-31777542-C-A
• rs2062008409
• NM_012112.5:c.786C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-31777542-C-A
• chr20-31777542-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_012112.5(TPX2):​c.786C>A​(p.Phe262Leu) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F262F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TPX2 NM_012112.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 0 publications found

Genes affected

TPX2 (HGNC:1249): (TPX2 microtubule nucleation factor) Enables importin-alpha family protein binding activity and protein kinase binding activity. Involved in activation of protein kinase activity; microtubule cytoskeleton organization; and negative regulation of microtubule depolymerization. Located in intercellular bridge; mitotic spindle; and nucleoplasm. Colocalizes with spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

TPX2 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.792

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012112.5. 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
	TPX2	NM_012112.5	MANE Select	c.786C>A	p.Phe262Leu	missense	Exon 9 of 18	NP_036244.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPX2	ENST00000300403.11	TSL:1 MANE Select	c.786C>A	p.Phe262Leu	missense	Exon 9 of 18	ENSP00000300403.6	Q9ULW0-1
	TPX2	ENST00000340513.4	TSL:1	c.786C>A	p.Phe262Leu	missense	Exon 9 of 19	ENSP00000341145.4	Q9ULW0-2
	TPX2	ENST00000934062.1		c.786C>A	p.Phe262Leu	missense	Exon 9 of 19	ENSP00000604121.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.033
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.4
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.53
Sift	Benign	0.031	D
Sift4G	Benign	0.31	T
Polyphen		1.0	D
Vest4		0.79
MutPred		0.41		Gain of MoRF binding (P = 0.102)
MVP		0.83
MPC		0.60
ClinPred		1.0	D
GERP RS		0.0076
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.45
gMVP		0.29
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs2062008409; hg19: chr20-30365345; COSMIC: COSV55919521;