Variant chr10-122083671-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_206862.4(TACC2):c.1171G>C(p.Val391Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TACC2
NM_206862.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.710

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08220446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACC2	NM_206862.4 linkuse as main transcript	c.1171G>C	p.Val391Leu	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.1171G>C	p.Val391Leu	missense_variant	4/23	1	NM_206862.4	ENSP00000358001		O95359-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459590

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726218

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 07, 2023

The c.1171G>C (p.V391L) alteration is located in exon 4 (coding exon 3) of the TACC2 gene. This alteration results from a G to C substitution at nucleotide position 1171, causing the valine (V) at amino acid position 391 to be replaced by a leucine (L). 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

0.28

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

T;T;T;T;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.74

.;.;T;T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.082

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.7

L;.;.;L;.

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.44

N;N;N;N;N

REVEL

Benign

0.046

Sift

Uncertain

0.0030

D;D;D;D;D

Sift4G

Uncertain

0.030

D;T;T;D;T

Polyphen

0.61

P;P;P;P;P

Vest4

0.097

MutPred

0.25

Gain of catalytic residue at V391 (P = 0.232);Gain of catalytic residue at V391 (P = 0.232);Gain of catalytic residue at V391 (P = 0.232);Gain of catalytic residue at V391 (P = 0.232);Gain of catalytic residue at V391 (P = 0.232);

MVP

0.33

MPC

0.13

ClinPred

0.20

GERP RS

3.8

Varity_R

0.11

gMVP

0.078

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over