chr10-122220593-G-A

Variant names:

• chr10-122220593-G-A
• rs6585804
• NM_206862.4:c.7546+3765G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206862.4(TACC2):​c.7546+3765G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,096 control chromosomes in the GnomAD database, including 20,878 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 0.51 (20878 hom., cov: 33)
• Consequence: TACC2 NM_206862.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 6 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 (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACC2	NM_206862.4	c.7546+3765G>A		intron_variant	Intron 11 of 22	ENST00000369005.6	NP_996744.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACC2	ENST00000369005.6	c.7546+3765G>A		intron_variant	Intron 11 of 22	1	NM_206862.4	ENSP00000358001.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77780 AN: 151978 Hom.: 20846 Cov.: 33

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.538

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.512 AC: 77864 AN: 152096 Hom.: 20878 Cov.: 33 AF XY: 0.521 AC XY: 38720 AN XY: 74364

African (AFR) AF: 0.388 AC: 16076 AN: 41464

American (AMR) AF: 0.636 AC: 9724 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1896 AN: 3468

East Asian (EAS) AF: 0.873 AC: 4529 AN: 5190

South Asian (SAS) AF: 0.697 AC: 3350 AN: 4806

European-Finnish (FIN) AF: 0.534 AC: 5655 AN: 10590

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34986 AN: 67974

Other (OTH) AF: 0.544 AC: 1149 AN: 2114

Alfa AF: 0.521 Hom.: 89836

Bravo AF: 0.518

Asia WGS AF: 0.776 AC: 2700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.11
DANN	Benign	0.57
PhyloP100		-1.1
Mutation Taster		=100/0	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: rs6585804; hg19: chr10-123980108;