chr10-122211207-T-C

Variant names:

• chr10-122211207-T-C
• rs2295876
• NM_206862.4:c.6782T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000369005.6(TACC2):​c.6782T>C​(p.Leu2261Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00392 in 1,613,668 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0029 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (26 hom.)
• Consequence: TACC2 ENST00000369005.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08
• Publications: 20 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0050789714).
• BS2: High AC in GnomAd4 at 441 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369005.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACC2	NM_206862.4	MANE Select	c.6782T>C	p.Leu2261Pro	missense	Exon 9 of 23	NP_996744.4
	TACC2	NM_001438364.1		c.6707T>C	p.Leu2236Pro	missense	Exon 9 of 23	NP_001425293.1
	TACC2	NM_001291877.2		c.6794T>C	p.Leu2265Pro	missense	Exon 8 of 20	NP_001278806.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACC2	ENST00000369005.6	TSL:1 MANE Select	c.6782T>C	p.Leu2261Pro	missense	Exon 9 of 23	ENSP00000358001.1
	TACC2	ENST00000515273.5	TSL:1	c.6794T>C	p.Leu2265Pro	missense	Exon 8 of 20	ENSP00000424467.1
	TACC2	ENST00000515603.5	TSL:1	c.6647T>C	p.Leu2216Pro	missense	Exon 8 of 20	ENSP00000427618.1

Frequencies

GnomAD3 genomes AF: 0.00290 AC: 441 AN: 151872 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000677

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000853

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00889

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00427

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.00315 AC: 791 AN: 251058 AF XY: 0.00304

Gnomad AFR exome AF: 0.000739

Gnomad AMR exome AF: 0.00122

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00864

Gnomad NFE exome AF: 0.00409

Gnomad OTH exome AF: 0.00474

GnomAD4 exome AF: 0.00403 AC: 5884 AN: 1461676 Hom.: 26 Cov.: 33 AF XY: 0.00388 AC XY: 2818 AN XY: 727100

African (AFR) AF: 0.000747 AC: 25 AN: 33470

American (AMR) AF: 0.00150 AC: 67 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00280 AC: 73 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00139 AC: 120 AN: 86210

European-Finnish (FIN) AF: 0.00689 AC: 368 AN: 53418

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00450 AC: 5004 AN: 1111936

Other (OTH) AF: 0.00369 AC: 223 AN: 60380

GnomAD4 genome AF: 0.00290 AC: 441 AN: 151992 Hom.: 3 Cov.: 32 AF XY: 0.00273 AC XY: 203 AN XY: 74280

African (AFR) AF: 0.000675 AC: 28 AN: 41484

American (AMR) AF: 0.000852 AC: 13 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4794

European-Finnish (FIN) AF: 0.00889 AC: 94 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00427 AC: 290 AN: 67958

Other (OTH) AF: 0.00238 AC: 5 AN: 2104

Alfa AF: 0.000452 Hom.: 660

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00389 AC: 15

ExAC AF: 0.00290 AC: 352

EpiCase AF: 0.00354

EpiControl AF: 0.00403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.15
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.050	T
Polyphen		1.0	D
Vest4		0.78
MVP		0.60
MPC		0.64
ClinPred		0.029	T
GERP RS		5.0
PromoterAI		-0.0057	Neutral
Varity_R		0.22
gMVP		0.19
Mutation Taster		=289/11	polymorphism

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: rs2295876; hg19: chr10-123970722; COSMIC: COSV53280614; COSMIC: COSV53280614;