chr10-122083240-A-C

Variant names:

• chr10-122083240-A-C
• rs151218566
• NM_206862.4:c.740A>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_206862.4(TACC2):​c.740A>C​(p.Gln247Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 1,613,434 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (8 hom.)
• Consequence: TACC2 NM_206862.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.43
• Publications: 5 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0042963624).
• BP6: Variant 10-122083240-A-C is Benign according to our data. Variant chr10-122083240-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 718876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 350 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACC2	NM_206862.4	MANE Select	c.740A>C	p.Gln247Pro	missense	Exon 4 of 23	NP_996744.4	O95359-4
	TACC2	NM_001438364.1		c.800A>C	p.Gln267Pro	missense	Exon 5 of 23	NP_001425293.1
	TACC2	NM_001291877.2		c.740A>C	p.Gln247Pro	missense	Exon 4 of 20	NP_001278806.2	E9PBC6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACC2	ENST00000369005.6	TSL:1 MANE Select	c.740A>C	p.Gln247Pro	missense	Exon 4 of 23	ENSP00000358001.1	O95359-4
	TACC2	ENST00000515273.5	TSL:1	c.740A>C	p.Gln247Pro	missense	Exon 4 of 20	ENSP00000424467.1	E9PBC6
	TACC2	ENST00000515603.5	TSL:1	c.740A>C	p.Gln247Pro	missense	Exon 4 of 20	ENSP00000427618.1	E7EMZ9

Frequencies

GnomAD3 genomes AF: 0.00230 AC: 350 AN: 151992 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000846

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00382

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00270 AC: 678 AN: 250690 AF XY: 0.00266

Gnomad AFR exome AF: 0.000682

Gnomad AMR exome AF: 0.00220

Gnomad ASJ exome AF: 0.000897

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00319

Gnomad NFE exome AF: 0.00396

Gnomad OTH exome AF: 0.00426

GnomAD4 exome AF: 0.00300 AC: 4385 AN: 1461324 Hom.: 8 Cov.: 39 AF XY: 0.00299 AC XY: 2177 AN XY: 726958

African (AFR) AF: 0.000478 AC: 16 AN: 33480

American (AMR) AF: 0.00242 AC: 108 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000919 AC: 24 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00103 AC: 89 AN: 86256

European-Finnish (FIN) AF: 0.00319 AC: 169 AN: 52924

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.00339 AC: 3769 AN: 1111968

Other (OTH) AF: 0.00338 AC: 204 AN: 60384

GnomAD4 genome AF: 0.00230 AC: 350 AN: 152110 Hom.: 0 Cov.: 32 AF XY: 0.00215 AC XY: 160 AN XY: 74374

African (AFR) AF: 0.000843 AC: 35 AN: 41494

American (AMR) AF: 0.00111 AC: 17 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4806

European-Finnish (FIN) AF: 0.00273 AC: 29 AN: 10610

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

European-Non Finnish (NFE) AF: 0.00382 AC: 260 AN: 67984

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00372 Hom.: 8

Bravo AF: 0.00214

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00285 AC: 11

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00372 AC: 32

ExAC AF: 0.00258 AC: 313

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00534

EpiControl AF: 0.00373

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.2
DANN	Benign	0.69
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.4
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.020
Sift	Benign	0.57	T
Sift4G	Benign	0.39	T
Polyphen		0.0030	B
Vest4		0.18
MVP		0.33
MPC		0.12
ClinPred		0.0010	T
GERP RS		3.0
Varity_R		0.076
gMVP		0.062
Mutation Taster		=99/1	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: rs151218566; hg19: chr10-123842755; COSMIC: COSV108165630; COSMIC: COSV108165630;