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. Variant got 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPX2	NM_012112.5	c.786C>A	p.Phe262Leu	missense_variant	Exon 9 of 18	ENST00000300403.11	NP_036244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPX2	ENST00000300403.11	c.786C>A	p.Phe262Leu	missense_variant	Exon 9 of 18	1	NM_012112.5	ENSP00000300403.6
TPX2	ENST00000340513.4	c.786C>A	p.Phe262Leu	missense_variant	Exon 9 of 19	1		ENSP00000341145.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-4.5	D;D
REVEL	Uncertain	0.53
Sift	Benign	0.031	D;D
Sift4G	Benign	0.31	T;T
Polyphen		1.0	D;.
Vest4		0.79
MutPred		0.41		Gain of MoRF binding (P = 0.102);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

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