Variant chr10-122211207-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_206862.4(TACC2):c.6782T>C(p.Leu2261Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00392 in 1,613,668 control chromosomes in the GnomAD database, including 29 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. L2261H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0029 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 26 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050789714).

BS2

High AC in GnomAd4 at 441 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACC2	NM_206862.4 linkuse as main transcript	c.6782T>C	p.Leu2261Pro	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>C	p.Leu2261Pro	missense_variant	9/23	1	NM_206862.4	ENSP00000358001.1		O95359-4

Frequencies

GnomAD3 genomes

AF:

0.00290

AC:

441

AN:

151872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000677

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000853

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00889

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00427

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00315

AC:

791

AN:

251058

Hom.:

AF XY:

0.00304

AC XY:

413

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.000739

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.00864

Gnomad NFE exome

AF:

0.00409

Gnomad OTH exome

AF:

0.00474

GnomAD4 exome

AF:

0.00403

AC:

5884

AN:

1461676

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

2818

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00150

Gnomad4 ASJ exome

AF:

0.00280

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00139

Gnomad4 FIN exome

AF:

0.00689

Gnomad4 NFE exome

AF:

0.00450

Gnomad4 OTH exome

AF:

0.00369

GnomAD4 genome

AF:

0.00290

AC:

441

AN:

151992

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

203

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.000675

Gnomad4 AMR

AF:

0.000852

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00889

Gnomad4 NFE

AF:

0.00427

Gnomad4 OTH

AF:

0.00238

Alfa

AF:

0.000452

Hom.:

660

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00389

AC:

ExAC

AF:

0.00290

AC:

352

EpiCase

AF:

0.00354

EpiControl

AF:

0.00403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

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

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

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

M_CAP

Benign

0.019

MetaRNN

Benign

0.0051

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

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

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.7

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

REVEL

Benign

0.15

Sift

Uncertain

0.0040

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

Sift4G

Uncertain

0.050

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

0.78

MVP

0.60

MPC

0.64

ClinPred

0.029

GERP RS

5.0

Varity_R

0.22

gMVP

0.19

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