chr20-56387716-T-G

Variant names:

• chr20-56387716-T-G
• rs2064863
• NM_198437.3:c.42+440A>C

Variant summary

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

The NM_198437.3(AURKA):​c.42+440A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,094 control chromosomes in the GnomAD database, including 18,057 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 0.46 (18057 hom., cov: 33)
• Consequence: AURKA NM_198437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.584 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.42+440A>C		intron	N/A	NP_940839.1	O14965
	AURKA	NM_001424418.1		c.144+440A>C		intron	N/A	NP_001411347.1
	AURKA	NM_001424419.1		c.144+440A>C		intron	N/A	NP_001411348.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	ENST00000395915.8	TSL:1 MANE Select	c.42+440A>C		intron	N/A	ENSP00000379251.3	O14965
	AURKA	ENST00000312783.10	TSL:1	c.42+440A>C		intron	N/A	ENSP00000321591.6	O14965
	AURKA	ENST00000347343.6	TSL:1	c.42+440A>C		intron	N/A	ENSP00000216911.2	O14965

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69400 AN: 151976 Hom.: 18053 Cov.: 33

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.499

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.456 AC: 69405 AN: 152094 Hom.: 18057 Cov.: 33 AF XY: 0.452 AC XY: 33639 AN XY: 74352

African (AFR) AF: 0.210 AC: 8723 AN: 41498

American (AMR) AF: 0.544 AC: 8298 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2079 AN: 3470

East Asian (EAS) AF: 0.191 AC: 989 AN: 5180

South Asian (SAS) AF: 0.470 AC: 2266 AN: 4824

European-Finnish (FIN) AF: 0.497 AC: 5252 AN: 10568

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 40000 AN: 67988

Other (OTH) AF: 0.497 AC: 1044 AN: 2102

Alfa AF: 0.547 Hom.: 45874

Bravo AF: 0.447

Asia WGS AF: 0.342 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.38
DANN	Benign	0.35
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2064863; hg19: chr20-54962772; COSMIC: COSV53858294; COSMIC: COSV53858294;