rs2295879

chr10-122237461-G-Achr10-122237461-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206862.4(TACC2):c.8194G>A(p.Ala2732Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,613,346 control chromosomes in the GnomAD database, including 78,327 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 0.27 (5938 hom., cov: 32)
  • Exomes 𝑓: 0.31 (72389 hom.)
• Consequence: TACC2 NM_206862.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.747

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00278607).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TACC2	NM_206862.4	c.8194G>A	p.Ala2732Thr	missense_variant	17/23	ENST00000369005.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TACC2	ENST00000369005.6	c.8194G>A	p.Ala2732Thr	missense_variant	17/23	1	NM_206862.4

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40877 AN: 151872 Hom.: 5923 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.314

GnomAD3 exomes AF: 0.307 AC: 77115 AN: 251042 Hom.: 12410 AF XY: 0.314 AC XY: 42603 AN XY: 135676

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.306

Gnomad ASJ exome AF: 0.400

Gnomad EAS exome AF: 0.235

Gnomad SAS exome AF: 0.395

Gnomad FIN exome AF: 0.307

Gnomad NFE exome AF: 0.308

Gnomad OTH exome AF: 0.321

GnomAD4 exome AF: 0.311 AC: 454846 AN: 1461356 Hom.: 72389 Cov.: 38 AF XY: 0.315 AC XY: 228710 AN XY: 726968

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.310

Gnomad4 ASJ exome AF: 0.401

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.394

Gnomad4 FIN exome AF: 0.305

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.320

GnomAD4 genome AF: 0.269 AC: 40909 AN: 151990 Hom.: 5938 Cov.: 32 AF XY: 0.271 AC XY: 20150 AN XY: 74284

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.321

Alfa AF: 0.310 Hom.: 19442

Bravo AF: 0.260

TwinsUK AF: 0.330 AC: 1223

ALSPAC AF: 0.319 AC: 1228

ESP6500AA AF: 0.159 AC: 701

ESP6500EA AF: 0.302 AC: 2598

ExAC AF: 0.303 AC: 36750

Asia WGS AF: 0.351 AC: 1224 AN: 3478

EpiCase AF: 0.312

EpiControl AF: 0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	0.079
Dann	Benign	0.71
DEOGEN2	Benign	0.017	T;.;T;T;T;.;T;.;.;.;.;T;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.047	N
MetaRNN	Benign	0.0028	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.34	N;.;.;.;N;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P;P;P;P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.020	N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.042
Sift	Benign	0.39	T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.99	T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0	B;B;B;B;B;B;B;.;B;B;.;B;B;.
Vest4		0.019
MPC		0.095
ClinPred		0.00051	T
GERP RS		-6.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.019
gMVP		0.25

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

Other links and lift over

dbSNP: rs2295879; hg19: chr10-123996976; COSMIC: COSV53279154; COSMIC: COSV53279154;