Variant 10-122082849-C-G 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.349C>G(p.Pro117Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,430 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

TACC2
NM_206862.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.287

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04511419).

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACC2	NM_206862.4 linkuse as main transcript	c.349C>G	p.Pro117Ala	missense_variant	4/23	ENST00000369005.6	NP_996744.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TACC2	ENST00000369005.6 linkuse as main transcript	c.349C>G	p.Pro117Ala	missense_variant	4/23	1	NM_206862.4	ENSP00000358001		O95359-4

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250804

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1461366

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152064

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.000266

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2022

The c.349C>G (p.P117A) alteration is located in exon 4 (coding exon 3) of the TACC2 gene. This alteration results from a C to G substitution at nucleotide position 349, causing the proline (P) at amino acid position 117 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.9

DANN

Benign

0.85

DEOGEN2

Benign

0.024

T;T;T;T;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.63

.;.;T;T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.045

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.;.;L;.

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.2

N;N;N;N;N

REVEL

Benign

0.018

Sift

Uncertain

0.019

D;D;D;D;D

Sift4G

Benign

0.17

T;T;T;T;T

Polyphen

0.0020

B;B;B;B;B

Vest4

0.18

MVP

0.25

MPC

0.11

ClinPred

0.014

GERP RS

-1.8

Varity_R

0.032

gMVP

0.082

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