Variant rs2295876 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.6782T>A(p.Leu2261His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,620 control chromosomes in the GnomAD database, including 12,307 homozygotes. In-silico tool predicts 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.092 ( 776 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11531 hom. )

Consequence

TACC2
NM_206862.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.08

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:

TACC2 (HGNC:):

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=0.0013515353).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACC2	NM_206862.4 linkuse as main transcript	c.6782T>A	p.Leu2261His	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 linkuse as main transcript	c.6782T>A	p.Leu2261His	missense_variant	9/23	1	NM_206862.4	ENSP00000358001.1		O95359-4

Frequencies

GnomAD3 genomes

AF:

0.0924

AC:

14038

AN:

151854

Hom.:

774

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0240

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.0998

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.0961

GnomAD3 exomes

AF:

0.120

AC:

30153

AN:

251058

Hom.:

1993

AF XY:

0.123

AC XY:

16717

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.0225

Gnomad AMR exome

AF:

0.140

Gnomad ASJ exome

AF:

0.0905

Gnomad EAS exome

AF:

0.128

Gnomad SAS exome

AF:

0.156

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.122

AC:

178089

AN:

1461646

Hom.:

11531

Cov.:

AF XY:

0.123

AC XY:

89673

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.0180

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.0914

Gnomad4 EAS exome

AF:

0.100

Gnomad4 SAS exome

AF:

0.155

Gnomad4 FIN exome

AF:

0.113

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.115

GnomAD4 genome

AF:

0.0924

AC:

14041

AN:

151974

Hom.:

776

Cov.:

AF XY:

0.0934

AC XY:

6937

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.0239

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.0998

Gnomad4 EAS

AF:

0.120

Gnomad4 SAS

AF:

0.161

Gnomad4 FIN

AF:

0.107

Gnomad4 NFE

AF:

0.120

Gnomad4 OTH

AF:

0.0951

Alfa

AF:

0.108

Hom.:

660

Bravo

AF:

0.0897

TwinsUK

AF:

0.128

AC:

473

ALSPAC

AF:

0.123

AC:

475

ESP6500AA

AF:

0.0266

AC:

117

ESP6500EA

AF:

0.124

AC:

1067

ExAC

AF:

0.119

AC:

14490

EpiCase

AF:

0.119

EpiControl

AF:

0.116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.023

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

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.87

.;.;.;D;D;D;D;D;D;D;D;D

MetaRNN

Benign

0.0014

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

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

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.5

N;D;N;N;N;D;N;D;D;D;D;N

REVEL

Benign

0.061

Sift

Uncertain

0.0050

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

Sift4G

Benign

0.075

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

Polyphen

1.0

D;D;D;D;D;D;D;D;.;D;D;D

Vest4

0.62

MPC

0.57

ClinPred

0.033

GERP RS

5.0

Varity_R

0.12

gMVP

0.16

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