rs2230743

Variant names:

• chr20-56386265-G-A
• rs2230743
• NM_198437.3:c.311C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-56386265-G-A
• chr20-56386265-G-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_198437.3(AURKA):​c.311C>T​(p.Ser104Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000343 in 1,614,260 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00025 (5 hom.)
• Consequence: AURKA NM_198437.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.38
• Publications: 10 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004119545).
• BP6: Variant 20-56386265-G-A is Benign according to our data. Variant chr20-56386265-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3033554.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 194 AD gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	NM_198437.3	MANE Select	c.311C>T	p.Ser104Leu	missense	Exon 3 of 9	NP_940839.1
	AURKA	NM_001424418.1		c.413C>T	p.Ser138Leu	missense	Exon 5 of 11	NP_001411347.1
	AURKA	NM_001424419.1		c.413C>T	p.Ser138Leu	missense	Exon 5 of 11	NP_001411348.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	ENST00000395915.8	TSL:1 MANE Select	c.311C>T	p.Ser104Leu	missense	Exon 3 of 9	ENSP00000379251.3
	AURKA	ENST00000312783.10	TSL:1	c.311C>T	p.Ser104Leu	missense	Exon 4 of 10	ENSP00000321591.6
	AURKA	ENST00000347343.6	TSL:1	c.311C>T	p.Ser104Leu	missense	Exon 3 of 9	ENSP00000216911.2

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 194 AN: 152250 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00415

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000994 AC: 250 AN: 251462 AF XY: 0.000758

Gnomad AFR exome AF: 0.00492

Gnomad AMR exome AF: 0.00483

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000246 AC: 359 AN: 1461892 Hom.: 5 Cov.: 30 AF XY: 0.000226 AC XY: 164 AN XY: 727246

African (AFR) AF: 0.00514 AC: 172 AN: 33480

American (AMR) AF: 0.00369 AC: 165 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112012

Other (OTH) AF: 0.000215 AC: 13 AN: 60396

GnomAD4 genome AF: 0.00127 AC: 194 AN: 152368 Hom.: 1 Cov.: 33 AF XY: 0.00109 AC XY: 81 AN XY: 74512

African (AFR) AF: 0.00414 AC: 172 AN: 41578

American (AMR) AF: 0.00131 AC: 20 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000554 Hom.: 0

Bravo AF: 0.00173

ESP6500AA AF: 0.00454 AC: 20

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00101 AC: 123

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	AURKA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.82	T
PhyloP100		3.4
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.079
Sift	Benign	0.13	T
Sift4G	Benign	0.15	T
Polyphen		0.0020	B
Vest4		0.056
MVP		0.40
ClinPred		0.024	T
GERP RS		5.2
gMVP		0.24
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs2230743; hg19: chr20-54961321; COSMIC: COSV57168158; COSMIC: COSV57168158;