Variant rs2295874 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_206862.4(TACC2):c.6629C>T(p.Ala2210Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,612,502 control chromosomes in the GnomAD database, including 10,813 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.099 ( 767 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10046 hom. )

Consequence

TACC2
NM_206862.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99

Variant links:

Genes affected

TACC2 (HGNC:11523): (transforming acidic coiled-coil containing protein 2) Transforming acidic coiled-coil proteins are a conserved family of centrosome- and microtubule-interacting proteins that are implicated in cancer. This gene encodes a protein that concentrates at centrosomes throughout the cell cycle. This gene lies within a chromosomal region associated with tumorigenesis. Expression of this gene is induced by erythropoietin and is thought to affect the progression of breast tumors. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

TACC2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016453862).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACC2	NM_206862.4 link	c.6629C>T	p.Ala2210Val	missense_variant	9/23	ENST00000369005.6	NP_996744.4	O95359-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TACC2	ENST00000369005.6 link	c.6629C>T	p.Ala2210Val	missense_variant	9/23	1	NM_206862.4	ENSP00000358001.1		O95359-4

Frequencies

GnomAD3 genomes

AF:

0.0986

AC:

14993

AN:

152118

Hom.:

765

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0675

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.0977

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.0766

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.0987

GnomAD3 exomes

AF:

0.116

AC:

28663

AN:

248000

Hom.:

1795

AF XY:

0.118

AC XY:

15863

AN XY:

134520

show subpopulations

Gnomad AFR exome

AF:

0.0666

Gnomad AMR exome

AF:

0.140

Gnomad ASJ exome

AF:

0.0905

Gnomad EAS exome

AF:

0.128

Gnomad SAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.0836

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.114

AC:

166745

AN:

1460266

Hom.:

10046

Cov.:

AF XY:

0.116

AC XY:

84217

AN XY:

726384

show subpopulations

Gnomad4 AFR exome

AF:

0.0689

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.0906

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.0827

Gnomad4 NFE exome

AF:

0.114

Gnomad4 OTH exome

AF:

0.112

GnomAD4 genome

AF:

0.0985

AC:

15002

AN:

152236

Hom.:

767

Cov.:

AF XY:

0.0981

AC XY:

7303

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0675

Gnomad4 AMR

AF:

0.120

Gnomad4 ASJ

AF:

0.0977

Gnomad4 EAS

AF:

0.120

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.0766

Gnomad4 NFE

AF:

0.110

Gnomad4 OTH

AF:

0.0981

Alfa

AF:

0.106

Hom.:

1537

Bravo

AF:

0.100

TwinsUK

AF:

0.113

AC:

420

ALSPAC

AF:

0.114

AC:

438

ESP6500AA

AF:

0.0707

AC:

311

ESP6500EA

AF:

0.113

AC:

976

ExAC

AF:

0.114

AC:

13876

Asia WGS

AF:

0.128

AC:

448

AN:

3478

EpiCase

AF:

0.111

EpiControl

AF:

0.107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.3

DANN

Benign

0.31

DEOGEN2

Benign

0.015

T;.;T;T;T;.;T;.;.;T;.;T;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.81

.;.;.;T;T;T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0016

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.;.;.;L;.;.;.;.;.;.;.;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.080

N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.036

Sift

Benign

0.20

T;T;T;T;T;T;T;T;T;T;T;T;D

Sift4G

Benign

0.23

T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.24

B;B;B;B;B;B;B;B;.;B;B;B;.

Vest4

0.064

MPC

0.15

ClinPred

0.0041

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.016

gMVP

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over