chr20-56386407-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_198437.3(AURKA):c.169A>G(p.Ile57Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 1,613,986 control chromosomes in the GnomAD database, including 575,145 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.84 ( 54283 hom., cov: 31)

Exomes 𝑓: 0.84 ( 520862 hom. )

Consequence

AURKA
NM_198437.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.556

Publications

124 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.0621073E-7).

BP6

Variant 20-56386407-T-C is Benign according to our data. Variant chr20-56386407-T-C is described in ClinVar as Benign. ClinVar VariationId is 3059051.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKA	NM_198437.3 link	c.169A>G	p.Ile57Val	missense_variant	Exon 3 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.169A>G	p.Ile57Val	missense_variant	Exon 3 of 9	1	NM_198437.3	ENSP00000379251.3		O14965

Frequencies

GnomAD3 genomes

AF:

0.844

AC:

128366

AN:

152010

Hom.:

54229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.838

Gnomad AMI

AF:

0.892

Gnomad AMR

AF:

0.887

Gnomad ASJ

AF:

0.865

Gnomad EAS

AF:

0.881

Gnomad SAS

AF:

0.856

Gnomad FIN

AF:

0.810

Gnomad MID

AF:

0.877

Gnomad NFE

AF:

0.838

Gnomad OTH

AF:

0.860

GnomAD2 exomes

AF:

0.851

AC:

213970

AN:

251486

AF XY:

0.848

show subpopulations

Gnomad AFR exome

AF:

0.839

Gnomad AMR exome

AF:

0.916

Gnomad ASJ exome

AF:

0.853

Gnomad EAS exome

AF:

0.878

Gnomad FIN exome

AF:

0.807

Gnomad NFE exome

AF:

0.835

Gnomad OTH exome

AF:

0.842

GnomAD4 exome

AF:

0.844

AC:

1233537

AN:

1461858

Hom.:

520862

Cov.:

AF XY:

0.844

AC XY:

613833

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.834

AC:

27934

AN:

33480

American (AMR)

AF:

0.912

AC:

40766

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.858

AC:

22435

AN:

26136

East Asian (EAS)

AF:

0.871

AC:

34571

AN:

39700

South Asian (SAS)

AF:

0.858

AC:

73996

AN:

86258

European-Finnish (FIN)

AF:

0.810

AC:

43274

AN:

53420

Middle Eastern (MID)

AF:

0.835

AC:

4819

AN:

5768

European-Non Finnish (NFE)

AF:

0.840

AC:

934582

AN:

1111978

Other (OTH)

AF:

0.847

AC:

51160

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

13494

26989

40483

53978

67472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21134

42268

63402

84536

105670

<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:

0.845

AC:

128476

AN:

152128

Hom.:

54283

Cov.:

AF XY:

0.843

AC XY:

62696

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.838

AC:

34768

AN:

41488

American (AMR)

AF:

0.887

AC:

13570

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.865

AC:

3004

AN:

3472

East Asian (EAS)

AF:

0.880

AC:

4548

AN:

5166

South Asian (SAS)

AF:

0.855

AC:

4123

AN:

4820

European-Finnish (FIN)

AF:

0.810

AC:

8562

AN:

10568

Middle Eastern (MID)

AF:

0.884

AC:

260

AN:

294

European-Non Finnish (NFE)

AF:

0.838

AC:

57020

AN:

68004

Other (OTH)

AF:

0.856

AC:

1809

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1036

2071

3107

4142

5178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

888

1776

2664

3552

4440

<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:

0.840

Hom.:

263613

Bravo

AF:

0.850

TwinsUK

AF:

0.841

AC:

3119

ALSPAC

AF:

0.847

AC:

3265

ESP6500AA

AF:

0.838

AC:

3693

ESP6500EA

AF:

0.838

AC:

7203

ExAC

AF:

0.848

AC:

102977

Asia WGS

AF:

0.872

AC:

3034

AN:

3478

EpiCase

AF:

0.829

EpiControl

AF:

0.826

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AURKA-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.032

(source)

DANN

Benign

0.21

DEOGEN2

Benign

0.0047

.;.;.;.;.;.;.;.;T;.;T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.016

.;.;.;.;.;.;.;T;T;T;T;T;T

MetaRNN

Benign

6.1e-7

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.94

PhyloP100

-0.56

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.010

N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.031

Sift

Benign

1.0

T;T;T;T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T;T;T;.;.;.;.;.

Polyphen

0.0

.;.;.;.;.;.;.;B;B;B;B;B;.

Vest4

0.010

ClinPred

0.00020

GERP RS

2.0

gMVP

0.092

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over