10-122237461-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_206862.4(TACC2):​c.8194G>C​(p.Ala2732Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 32)
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08895254).

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.8194G>C	p.Ala2732Pro	missense	Exon 17 of 23	NP_996744.4
	TACC2	NM_001438364.1		c.8119G>C	p.Ala2707Pro	missense	Exon 17 of 23	NP_001425293.1
	TACC2	NM_001291877.2		c.7975G>C	p.Ala2659Pro	missense	Exon 14 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.8194G>C	p.Ala2732Pro	missense	Exon 17 of 23	ENSP00000358001.1
	TACC2	ENST00000515273.5	TSL:1	c.7975G>C	p.Ala2659Pro	missense	Exon 14 of 20	ENSP00000424467.1
	TACC2	ENST00000515603.5	TSL:1	c.7828G>C	p.Ala2610Pro	missense	Exon 14 of 20	ENSP00000427618.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.82
DANN	Benign	0.96
DEOGEN2	Benign	0.034	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.75
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.045
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.052	T
Polyphen		0.11	B
Vest4		0.19
MutPred		0.24		Gain of disorder (P = 0.0643)
MVP		0.45
MPC		0.20
ClinPred		0.24	T
GERP RS		-6.6
PromoterAI		-0.040	Neutral
Varity_R		0.11
gMVP		0.41
Mutation Taster		=86/14	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: rs2295879; hg19: chr10-123996976;