Genetic Variant AURKA:c.*423G>C (chr20-56369735-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198437.3(AURKA):c.*423G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 362,708 control chromosomes in the GnomAD database, including 30,747 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 0.42 ( 15924 hom., cov: 33)

Exomes 𝑓: 0.35 ( 14823 hom. )

Consequence

AURKA
NM_198437.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.631

Publications

27 publications found

Variant links:

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

AURKA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKA	NM_198437.3 link	c.*423G>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000395915.8	NP_940839.1	O14965

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKA	ENST00000395915.8 link	c.*423G>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_198437.3	ENSP00000379251.3		O14965

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

64163

AN:

151944

Hom.:

15872

Cov.:

show subpopulations

Gnomad AFR

AF:

0.669

Gnomad AMI

AF:

0.250

Gnomad AMR

AF:

0.427

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.634

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.394

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.389

GnomAD4 exome

AF:

0.346

AC:

72806

AN:

210644

Hom.:

14823

Cov.:

AF XY:

0.345

AC XY:

36322

AN XY:

105184

show subpopulations

African (AFR)

AF:

0.679

AC:

5908

AN:

8706

American (AMR)

AF:

0.458

AC:

4228

AN:

9224

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

2385

AN:

8276

East Asian (EAS)

AF:

0.645

AC:

11899

AN:

18436

South Asian (SAS)

AF:

0.389

AC:

7615

AN:

19600

European-Finnish (FIN)

AF:

0.341

AC:

1913

AN:

5612

Middle Eastern (MID)

AF:

0.335

AC:

334

AN:

996

European-Non Finnish (NFE)

AF:

0.269

AC:

33967

AN:

126258

Other (OTH)

AF:

0.337

AC:

4557

AN:

13536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

2203

4405

6608

8810

11013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

380

760

1140

1520

1900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.423

AC:

64272

AN:

152064

Hom.:

15924

Cov.:

AF XY:

0.428

AC XY:

31771

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.670

AC:

27766

AN:

41470

American (AMR)

AF:

0.427

AC:

6528

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

1012

AN:

3470

East Asian (EAS)

AF:

0.634

AC:

3275

AN:

5168

South Asian (SAS)

AF:

0.408

AC:

1964

AN:

4818

European-Finnish (FIN)

AF:

0.394

AC:

4159

AN:

10562

Middle Eastern (MID)

AF:

0.408

AC:

119

AN:

292

European-Non Finnish (NFE)

AF:

0.271

AC:

18402

AN:

67968

Other (OTH)

AF:

0.388

AC:

819

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1636

3271

4907

6542

8178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.168

Hom.:

295

Bravo

AF:

0.437

Asia WGS

AF:

0.521

AC:

1813

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

9.0

(source)

DANN

Benign

0.60

PhyloP100

0.63

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over