10-122211054-C-T

Variant names:

• chr10-122211054-C-T
• rs2295874
• NM_206862.4:c.6629C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206862.4(TACC2):​c.6629C>T​(p.Ala2210Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,612,502 control chromosomes in the GnomAD database, including 10,813 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 0.099 (767 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10046 hom.)
• Consequence: TACC2 NM_206862.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 17 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=0.0016453862).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACC2	NM_206862.4	c.6629C>T	p.Ala2210Val	missense_variant	Exon 9 of 23	ENST00000369005.6	NP_996744.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACC2	ENST00000369005.6	c.6629C>T	p.Ala2210Val	missense_variant	Exon 9 of 23	1	NM_206862.4	ENSP00000358001.1

Frequencies

GnomAD3 genomes AF: 0.0986 AC: 14993 AN: 152118 Hom.: 765 Cov.: 32

Gnomad AFR AF: 0.0675

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0977

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0766

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0987

GnomAD2 exomes AF: 0.116 AC: 28663 AN: 248000 AF XY: 0.118

Gnomad AFR exome AF: 0.0666

Gnomad AMR exome AF: 0.140

Gnomad ASJ exome AF: 0.0905

Gnomad EAS exome AF: 0.128

Gnomad FIN exome AF: 0.0836

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.114 AC: 166745 AN: 1460266 Hom.: 10046 Cov.: 32 AF XY: 0.116 AC XY: 84217 AN XY: 726384

African (AFR) AF: 0.0689 AC: 2303 AN: 33406

American (AMR) AF: 0.139 AC: 6168 AN: 44434

Ashkenazi Jewish (ASJ) AF: 0.0906 AC: 2354 AN: 25994

East Asian (EAS) AF: 0.101 AC: 3993 AN: 39688

South Asian (SAS) AF: 0.158 AC: 13587 AN: 85948

European-Finnish (FIN) AF: 0.0827 AC: 4412 AN: 53376

Middle Eastern (MID) AF: 0.112 AC: 645 AN: 5752

European-Non Finnish (NFE) AF: 0.114 AC: 126546 AN: 1111352

Other (OTH) AF: 0.112 AC: 6737 AN: 60316

GnomAD4 genome AF: 0.0985 AC: 15002 AN: 152236 Hom.: 767 Cov.: 32 AF XY: 0.0981 AC XY: 7303 AN XY: 74430

African (AFR) AF: 0.0675 AC: 2805 AN: 41544

American (AMR) AF: 0.120 AC: 1838 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0977 AC: 339 AN: 3470

East Asian (EAS) AF: 0.120 AC: 618 AN: 5162

South Asian (SAS) AF: 0.163 AC: 784 AN: 4822

European-Finnish (FIN) AF: 0.0766 AC: 813 AN: 10618

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7492 AN: 68012

Other (OTH) AF: 0.0981 AC: 207 AN: 2110

Alfa AF: 0.106 Hom.: 2181

Bravo AF: 0.100

TwinsUK AF: 0.113 AC: 420

ALSPAC AF: 0.114 AC: 438

ESP6500AA AF: 0.0707 AC: 311

ESP6500EA AF: 0.113 AC: 976

ExAC AF: 0.114 AC: 13876

Asia WGS AF: 0.128 AC: 448 AN: 3478

EpiCase AF: 0.111

EpiControl AF: 0.107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.3
DANN	Benign	0.31
DEOGEN2	Benign	0.015	T;.;T;T;T;.;T;.;.;T;.;T;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.81	.;.;.;T;T;T;T;T;T;T;T;T;T
MetaRNN	Benign	0.0016	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.;.;.;L;.;.;.;.;.;.;.;.
PhyloP100		2.0
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.080	N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.036
Sift	Benign	0.20	T;T;T;T;T;T;T;T;T;T;T;T;D
Sift4G	Benign	0.23	T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.24	B;B;B;B;B;B;B;B;.;B;B;B;.
Vest4		0.064
MPC		0.15
ClinPred		0.0041	T
GERP RS		2.7
PromoterAI		0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.016
gMVP		0.15
Mutation Taster		=294/6	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: rs2295874; hg19: chr10-123970569; COSMIC: COSV53280580; COSMIC: COSV53280580;