Variant 10-122083240-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_206862.4(TACC2):c.740A>C(p.Gln247Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 1,613,434 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 8 hom. )

Consequence

TACC2
NM_206862.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.43

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042963624).

BP6

Variant 10-122083240-A-C is Benign according to our data. Variant chr10-122083240-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 718876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 350 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACC2	NM_206862.4 link	c.740A>C	p.Gln247Pro	missense_variant	4/23	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.740A>C	p.Gln247Pro	missense_variant	4/23	1	NM_206862.4	ENSP00000358001.1		O95359-4

Frequencies

GnomAD3 genomes

AF:

0.00230

AC:

350

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000846

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00382

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00270

AC:

678

AN:

250690

Hom.:

AF XY:

0.00266

AC XY:

361

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.000682

Gnomad AMR exome

AF:

0.00220

Gnomad ASJ exome

AF:

0.000897

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00127

Gnomad FIN exome

AF:

0.00319

Gnomad NFE exome

AF:

0.00396

Gnomad OTH exome

AF:

0.00426

GnomAD4 exome

AF:

0.00300

AC:

4385

AN:

1461324

Hom.:

Cov.:

AF XY:

0.00299

AC XY:

2177

AN XY:

726958

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00242

Gnomad4 ASJ exome

AF:

0.000919

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00103

Gnomad4 FIN exome

AF:

0.00319

Gnomad4 NFE exome

AF:

0.00339

Gnomad4 OTH exome

AF:

0.00338

GnomAD4 genome

AF:

0.00230

AC:

350

AN:

152110

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

160

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.000843

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00273

Gnomad4 NFE

AF:

0.00382

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00393

Hom.:

Bravo

AF:

0.00214

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00258

AC:

313

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00534

EpiControl

AF:

0.00373

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	TACC2: BP4 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

3.2

DANN

Benign

0.69

DEOGEN2

Benign

0.015

T;T;T;T;T

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.40

.;.;T;T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.0043

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.81

L;.;.;L;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.16

N;N;N;N;N

REVEL

Benign

0.020

Sift

Benign

0.57

T;T;T;T;T

Sift4G

Benign

0.39

T;T;T;T;T

Polyphen

0.0030

B;B;B;B;B

Vest4

0.18

MVP

0.33

MPC

0.12

ClinPred

0.0010

GERP RS

3.0

Varity_R

0.076

gMVP

0.062

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over