20-56384240-G-C

Variant names:

• chr20-56384240-G-C
• rs2298016
• NM_198437.3:c.374+30C>G

Variant summary

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

The NM_198437.3(AURKA):​c.374+30C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,555,324 control chromosomes in the GnomAD database, including 52,681 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 0.25 (5492 hom., cov: 32)
  • Exomes 𝑓: 0.24 (47189 hom.)
• Consequence: AURKA NM_198437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739
• Publications: 15 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKA	NM_198437.3	c.374+30C>G		intron_variant	Intron 4 of 8	ENST00000395915.8	NP_940839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKA	ENST00000395915.8	c.374+30C>G		intron_variant	Intron 4 of 8	1	NM_198437.3	ENSP00000379251.3

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38500 AN: 151848 Hom.: 5477 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.253

GnomAD2 exomes AF: 0.292 AC: 72409 AN: 247606 AF XY: 0.289

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.352

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.672

Gnomad FIN exome AF: 0.293

Gnomad NFE exome AF: 0.226

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.245 AC: 343407 AN: 1403358 Hom.: 47189 Cov.: 26 AF XY: 0.247 AC XY: 172971 AN XY: 701538

African (AFR) AF: 0.217 AC: 6998 AN: 32284

American (AMR) AF: 0.344 AC: 15322 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4183 AN: 25794

East Asian (EAS) AF: 0.663 AC: 25993 AN: 39224

South Asian (SAS) AF: 0.330 AC: 28027 AN: 84926

European-Finnish (FIN) AF: 0.293 AC: 14853 AN: 50710

Middle Eastern (MID) AF: 0.233 AC: 1321 AN: 5662

European-Non Finnish (NFE) AF: 0.218 AC: 231949 AN: 1061798

Other (OTH) AF: 0.253 AC: 14761 AN: 58444

GnomAD4 genome AF: 0.254 AC: 38550 AN: 151966 Hom.: 5492 Cov.: 32 AF XY: 0.262 AC XY: 19430 AN XY: 74268

African (AFR) AF: 0.226 AC: 9359 AN: 41470

American (AMR) AF: 0.275 AC: 4204 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 564 AN: 3470

East Asian (EAS) AF: 0.660 AC: 3410 AN: 5164

South Asian (SAS) AF: 0.344 AC: 1658 AN: 4816

European-Finnish (FIN) AF: 0.308 AC: 3241 AN: 10522

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.226 AC: 15321 AN: 67942

Other (OTH) AF: 0.252 AC: 533 AN: 2114

Alfa AF: 0.160 Hom.: 465

Bravo AF: 0.253

Asia WGS AF: 0.471 AC: 1630 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.49
PhyloP100		-0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2298016; hg19: chr20-54959296; COSMIC: COSV57167229;