rs2295876

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-122211207-T-A
• chr10-122211207-T-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.6782T>A​(p.Leu2261His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,620 control chromosomes in the GnomAD database, including 12,307 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 0.092 (776 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11531 hom.)
• Consequence: TACC2 NM_206862.4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013515353).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206862.4. 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>A	p.Leu2261His	missense	Exon 9 of 23	NP_996744.4
	TACC2	NM_001438364.1		c.6707T>A	p.Leu2236His	missense	Exon 9 of 23	NP_001425293.1
	TACC2	NM_001291877.2		c.6794T>A	p.Leu2265His	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>A	p.Leu2261His	missense	Exon 9 of 23	ENSP00000358001.1
	TACC2	ENST00000515273.5	TSL:1	c.6794T>A	p.Leu2265His	missense	Exon 8 of 20	ENSP00000424467.1
	TACC2	ENST00000515603.5	TSL:1	c.6647T>A	p.Leu2216His	missense	Exon 8 of 20	ENSP00000427618.1

Frequencies

GnomAD3 genomes AF: 0.0924 AC: 14038 AN: 151854 Hom.: 774 Cov.: 32

Gnomad AFR AF: 0.0240

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0998

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0961

GnomAD2 exomes AF: 0.120 AC: 30153 AN: 251058 AF XY: 0.123

Gnomad AFR exome AF: 0.0225

Gnomad AMR exome AF: 0.140

Gnomad ASJ exome AF: 0.0905

Gnomad EAS exome AF: 0.128

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.121

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.122 AC: 178089 AN: 1461646 Hom.: 11531 Cov.: 33 AF XY: 0.123 AC XY: 89673 AN XY: 727080

African (AFR) AF: 0.0180 AC: 602 AN: 33470

American (AMR) AF: 0.139 AC: 6224 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 2387 AN: 26118

East Asian (EAS) AF: 0.100 AC: 3977 AN: 39700

South Asian (SAS) AF: 0.155 AC: 13401 AN: 86204

European-Finnish (FIN) AF: 0.113 AC: 6045 AN: 53416

Middle Eastern (MID) AF: 0.103 AC: 596 AN: 5768

European-Non Finnish (NFE) AF: 0.124 AC: 137919 AN: 1111920

Other (OTH) AF: 0.115 AC: 6938 AN: 60378

GnomAD4 genome AF: 0.0924 AC: 14041 AN: 151974 Hom.: 776 Cov.: 32 AF XY: 0.0934 AC XY: 6937 AN XY: 74270

African (AFR) AF: 0.0239 AC: 992 AN: 41480

American (AMR) AF: 0.113 AC: 1724 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0998 AC: 346 AN: 3468

East Asian (EAS) AF: 0.120 AC: 616 AN: 5136

South Asian (SAS) AF: 0.161 AC: 773 AN: 4794

European-Finnish (FIN) AF: 0.107 AC: 1128 AN: 10572

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8156 AN: 67954

Other (OTH) AF: 0.0951 AC: 200 AN: 2104

Alfa AF: 0.108 Hom.: 660

Bravo AF: 0.0897

TwinsUK AF: 0.128 AC: 473

ALSPAC AF: 0.123 AC: 475

ESP6500AA AF: 0.0266 AC: 117

ESP6500EA AF: 0.124 AC: 1067

ExAC AF: 0.119 AC: 14490

EpiCase AF: 0.119

EpiControl AF: 0.116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.1
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.061
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.075	T
Polyphen		1.0	D
Vest4		0.62
MPC		0.57
ClinPred		0.033	T
GERP RS		5.0
PromoterAI		-0.018	Neutral
Varity_R		0.12
gMVP		0.16
Mutation Taster		=289/11	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: rs2295876; hg19: chr10-123970722; COSMIC: COSV53280628; COSMIC: COSV53280628;