rs2180691

Variant names:

• chr20-56389305-G-A
• rs2180691
• NM_198437.3:c.-5-1103C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-56389305-G-A
• chr20-56389305-G-T

Variant summary

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

The NM_001424418.1(AURKA):​c.-376-521C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,866 control chromosomes in the GnomAD database, including 17,931 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 0.44 (17931 hom., cov: 31)
• Consequence: AURKA NM_001424418.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 6 publications found

Genes affected

AURKA (HGNC:11393): (aurora kinase A) The protein encoded by this gene is a cell cycle-regulated kinase that appears to be involved in microtubule formation and/or stabilization at the spindle pole during chromosome segregation. The encoded protein is found at the centrosome in interphase cells and at the spindle poles in mitosis. This gene may play a role in tumor development and progression. A processed pseudogene of this gene has been found on chromosome 1, and an unprocessed pseudogene has been found on chromosome 10. Multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

AURKA Gene-Disease associations (from GenCC):

• breast cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001424418.1. 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
	AURKA	NM_198437.3	MANE Select	c.-5-1103C>T		intron	N/A	NP_940839.1
	AURKA	NM_001424418.1		c.-376-521C>T		intron	N/A	NP_001411347.1
	AURKA	NM_001424419.1		c.-376-521C>T		intron	N/A	NP_001411348.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	ENST00000395915.8	TSL:1 MANE Select	c.-5-1103C>T		intron	N/A	ENSP00000379251.3
	AURKA	ENST00000312783.10	TSL:1	c.-5-1103C>T		intron	N/A	ENSP00000321591.6
	AURKA	ENST00000347343.6	TSL:1	c.-5-1103C>T		intron	N/A	ENSP00000216911.2

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66501 AN: 151746 Hom.: 17886 Cov.: 31

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.439 AC: 66598 AN: 151866 Hom.: 17931 Cov.: 31 AF XY: 0.439 AC XY: 32555 AN XY: 74220

African (AFR) AF: 0.746 AC: 30886 AN: 41406

American (AMR) AF: 0.373 AC: 5692 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1082 AN: 3466

East Asian (EAS) AF: 0.683 AC: 3518 AN: 5148

South Asian (SAS) AF: 0.402 AC: 1931 AN: 4800

European-Finnish (FIN) AF: 0.330 AC: 3481 AN: 10536

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18822 AN: 67938

Other (OTH) AF: 0.400 AC: 845 AN: 2110

Alfa AF: 0.322 Hom.: 19794

Bravo AF: 0.458

Asia WGS AF: 0.541 AC: 1884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.57
PhyloP100		-0.40
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: rs2180691; hg19: chr20-54964361;