rs2273535

Variant names:

• chr20-56386485-A-T
• rs2273535
• NM_198437.3:c.91T>A
• AURKA p.Phe31Ile

Your query was ambiguous. Multiple possible variants found:

• chr20-56386485-A-T
• chr20-56386485-A-C
• chr20-56386485-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198437.3(AURKA):​c.91T>A​(p.Phe31Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,613,914 control chromosomes in the GnomAD database, including 50,544 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4562 hom., cov: 33)
  • Exomes 𝑓: 0.24 (45982 hom.)
• Consequence: AURKA NM_198437.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: -0.555
• Publications: 215 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.5131277E-6).
• BP6: Variant 20-56386485-A-T is Benign according to our data. Variant chr20-56386485-A-T is described in ClinVar as Benign. ClinVar VariationId is 6642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198437.3. 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.91T>A	p.Phe31Ile	missense	Exon 3 of 9	NP_940839.1	O14965
	AURKA	NM_001424418.1		c.193T>A	p.Phe65Ile	missense	Exon 5 of 11	NP_001411347.1
	AURKA	NM_001424419.1		c.193T>A	p.Phe65Ile	missense	Exon 5 of 11	NP_001411348.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	ENST00000395915.8	TSL:1 MANE Select	c.91T>A	p.Phe31Ile	missense	Exon 3 of 9	ENSP00000379251.3	O14965
	AURKA	ENST00000312783.10	TSL:1	c.91T>A	p.Phe31Ile	missense	Exon 4 of 10	ENSP00000321591.6	O14965
	AURKA	ENST00000347343.6	TSL:1	c.91T>A	p.Phe31Ile	missense	Exon 3 of 9	ENSP00000216911.2	O14965

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33952 AN: 152018 Hom.: 4556 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.222

GnomAD2 exomes AF: 0.278 AC: 69789 AN: 251444 AF XY: 0.274

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.342

Gnomad ASJ exome AF: 0.158

Gnomad EAS exome AF: 0.677

Gnomad FIN exome AF: 0.269

Gnomad NFE exome AF: 0.218

Gnomad OTH exome AF: 0.248

GnomAD4 exome AF: 0.236 AC: 345594 AN: 1461776 Hom.: 45982 Cov.: 41 AF XY: 0.238 AC XY: 172899 AN XY: 727194

African (AFR) AF: 0.137 AC: 4576 AN: 33480

American (AMR) AF: 0.333 AC: 14911 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 4139 AN: 26134

East Asian (EAS) AF: 0.666 AC: 26429 AN: 39700

South Asian (SAS) AF: 0.309 AC: 26615 AN: 86252

European-Finnish (FIN) AF: 0.271 AC: 14490 AN: 53416

Middle Eastern (MID) AF: 0.213 AC: 1228 AN: 5768

European-Non Finnish (NFE) AF: 0.215 AC: 238709 AN: 1111908

Other (OTH) AF: 0.240 AC: 14497 AN: 60396

GnomAD4 genome AF: 0.223 AC: 33974 AN: 152138 Hom.: 4562 Cov.: 33 AF XY: 0.230 AC XY: 17118 AN XY: 74378

African (AFR) AF: 0.143 AC: 5922 AN: 41508

American (AMR) AF: 0.262 AC: 4014 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 534 AN: 3468

East Asian (EAS) AF: 0.664 AC: 3431 AN: 5166

South Asian (SAS) AF: 0.324 AC: 1562 AN: 4822

European-Finnish (FIN) AF: 0.277 AC: 2929 AN: 10568

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.219 AC: 14862 AN: 67994

Other (OTH) AF: 0.222 AC: 469 AN: 2114

Alfa AF: 0.181 Hom.: 932

Bravo AF: 0.222

Asia WGS AF: 0.453 AC: 1576 AN: 3478

EpiCase AF: 0.216

EpiControl AF: 0.211

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	AURKA-related disorder (1)
-	-	-	Colon cancer, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.59
DANN	Benign	0.76
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0000035	T
MetaSVM	Benign	-0.99	T
PhyloP100		-0.56
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.052
Sift	Benign	0.50	T
Sift4G	Benign	0.40	T
gMVP		0.14
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2273535;

hg19: chr20-54961541;

COSMIC: COSV57167236;