10-122082952-C-T

Variant names:

• chr10-122082952-C-T
• rs78149003
• NM_206862.4:c.452C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_206862.4(TACC2):​c.452C>T​(p.Ala151Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00621 in 1,612,914 control chromosomes in the GnomAD database, including 235 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (105 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (130 hom.)
• Consequence: TACC2 NM_206862.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.291

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002523601).
• BP6: Variant 10-122082952-C-T is Benign according to our data. Variant chr10-122082952-C-T is described in ClinVar as [Benign]. Clinvar id is 784170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACC2	NM_206862.4	c.452C>T	p.Ala151Val	missense_variant	Exon 4 of 23	ENST00000369005.6	NP_996744.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACC2	ENST00000369005.6	c.452C>T	p.Ala151Val	missense_variant	Exon 4 of 23	1	NM_206862.4	ENSP00000358001.1

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3366 AN: 152088 Hom.: 105 Cov.: 32

Gnomad AFR AF: 0.0636

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0270

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00204

Gnomad OTH AF: 0.0210

GnomAD2 exomes AF: 0.0105 AC: 2618 AN: 249398 AF XY: 0.00865

Gnomad AFR exome AF: 0.0626

Gnomad AMR exome AF: 0.0255

Gnomad ASJ exome AF: 0.0346

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00244

Gnomad OTH exome AF: 0.0125

GnomAD4 exome AF: 0.00456 AC: 6654 AN: 1460708 Hom.: 130 Cov.: 32 AF XY: 0.00436 AC XY: 3171 AN XY: 726656

Gnomad4 AFR exome AF: 0.0648 AC: 2168 AN: 33480

Gnomad4 AMR exome AF: 0.0254 AC: 1134 AN: 44722

Gnomad4 ASJ exome AF: 0.0336 AC: 877 AN: 26136

Gnomad4 EAS exome AF: 0.0000252 AC: 1 AN: 39700

Gnomad4 SAS exome AF: 0.00122 AC: 105 AN: 86258

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 52270

Gnomad4 NFE exome AF: 0.00147 AC: 1635 AN: 1111990

Gnomad4 Remaining exome AF: 0.0102 AC: 614 AN: 60384

GnomAD4 genome AF: 0.0221 AC: 3366 AN: 152206 Hom.: 105 Cov.: 32 AF XY: 0.0221 AC XY: 1643 AN XY: 74408

Gnomad4 AFR AF: 0.0635 AC: 0.0634695 AN: 0.0634695

Gnomad4 AMR AF: 0.0270 AC: 0.0270005 AN: 0.0270005

Gnomad4 ASJ AF: 0.0346 AC: 0.0345622 AN: 0.0345622

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00124 AC: 0.00124378 AN: 0.00124378

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.00204 AC: 0.00204364 AN: 0.00204364

Gnomad4 OTH AF: 0.0208 AC: 0.0208136 AN: 0.0208136

Alfa AF: 0.00922 Hom.: 37

Bravo AF: 0.0262

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.0488 AC: 215

ESP6500EA AF: 0.00233 AC: 20

ExAC AF: 0.00979 AC: 1189

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00344

EpiControl AF: 0.00391

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.33
DANN	Benign	0.83
DEOGEN2	Benign	0.015	T;T;T;T;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0053	N
LIST_S2	Benign	0.59	.;.;T;T;T
MetaRNN	Benign	0.0025	T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N;.;.;N;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.19	N;N;N;N;N
REVEL	Benign	0.046
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	0.17	T;T;T;T;T
Polyphen		0.0	B;B;B;B;B
Vest4		0.087
MPC		0.098
ClinPred		0.0035	T
GERP RS		-10
Varity_R		0.019
gMVP		0.061
Mutation Taster		=100/0	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

Publications

LitVar

Other links and lift over

dbSNP: rs78149003; hg19: chr10-123842467;