rs2295879

Variant names:

• chr10-122237461-G-A
• rs2295879
• NM_206862.4:c.8194G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-122237461-G-A
• chr10-122237461-G-C

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 38 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TACC2	NM_206862.4	c.8194G>A	p.Ala2732Thr	missense_variant	Exon 17 of 23	ENST00000369005.6	NP_996744.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACC2	ENST00000369005.6	c.8194G>A	p.Ala2732Thr	missense_variant	Exon 17 of 23	1	NM_206862.4	ENSP00000358001.1

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

GnomAD2 exomes AF: 0.307 AC: 77115 AN: 251042 AF XY: 0.314

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 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

African (AFR) AF: 0.148 AC: 4970 AN: 33474

American (AMR) AF: 0.310 AC: 13864 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 10471 AN: 26110

East Asian (EAS) AF: 0.230 AC: 9125 AN: 39682

South Asian (SAS) AF: 0.394 AC: 33954 AN: 86178

European-Finnish (FIN) AF: 0.305 AC: 16287 AN: 53386

Middle Eastern (MID) AF: 0.381 AC: 2199 AN: 5766

European-Non Finnish (NFE) AF: 0.310 AC: 344678 AN: 1111702

Other (OTH) AF: 0.320 AC: 19298 AN: 60366

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

African (AFR) AF: 0.153 AC: 6364 AN: 41462

American (AMR) AF: 0.305 AC: 4666 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1355 AN: 3468

East Asian (EAS) AF: 0.253 AC: 1302 AN: 5152

South Asian (SAS) AF: 0.381 AC: 1825 AN: 4790

European-Finnish (FIN) AF: 0.311 AC: 3281 AN: 10564

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21111 AN: 67964

Other (OTH) AF: 0.321 AC: 675 AN: 2106

Alfa AF: 0.301 Hom.: 34618

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
LIST_S2	Benign	0.53	.;.;.;T;T;T;T;T;T;T;T;T;T;T
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;.;.;.;.;.;.;.;.;.
PhyloP100		-0.75
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
PromoterAI		0.0039	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.019
gMVP		0.25
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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