rs200691895

Variant names:

• chr10-122050528-C-G
• NM_206862.4:c.124C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-122050528-C-G
• chr10-122050528-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_206862.4(TACC2):​c.124C>G​(p.Pro42Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P42S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TACC2 NM_206862.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053417534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACC2	NM_206862.4	c.124C>G	p.Pro42Ala	missense_variant	Exon 3 of 23	ENST00000369005.6	NP_996744.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACC2	ENST00000369005.6	c.124C>G	p.Pro42Ala	missense_variant	Exon 3 of 23	1	NM_206862.4	ENSP00000358001.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461772 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727186

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.13
DANN	Benign	0.76
DEOGEN2	Benign	0.015	T;.;T;T;T;.;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.0087	N
LIST_S2	Benign	0.59	.;.;.;T;T;T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.053	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;N;.;.;N;N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.52	N;N;N;N;N;N;N
REVEL	Benign	0.064
Sift	Uncertain	0.0080	D;D;D;D;D;D;D
Sift4G	Benign	1.0	T;T;T;T;T;T;T
Polyphen		0.028	B;B;B;B;B;B;B
Vest4		0.079
MutPred		0.10		Loss of glycosylation at P42 (P = 0.0422);Loss of glycosylation at P42 (P = 0.0422);Loss of glycosylation at P42 (P = 0.0422);Loss of glycosylation at P42 (P = 0.0422);Loss of glycosylation at P42 (P = 0.0422);Loss of glycosylation at P42 (P = 0.0422);Loss of glycosylation at P42 (P = 0.0422);
MVP		0.35
MPC		0.11
ClinPred		0.045	T
GERP RS		-0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.023
gMVP		0.074

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-123810043;