chr20-56378228-T-G

Variant names:

• chr20-56378228-T-G
• rs6099122
• NM_198437.3:c.705+3205A>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.705+3205A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,142 control chromosomes in the GnomAD database, including 2,099 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 0.11 (2099 hom., cov: 32)
• Consequence: AURKA NM_198437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKA	NM_198437.3	c.705+3205A>C		intron_variant	Intron 6 of 8	ENST00000395915.8	NP_940839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKA	ENST00000395915.8	c.705+3205A>C		intron_variant	Intron 6 of 8	1	NM_198437.3	ENSP00000379251.3

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16201 AN: 152024 Hom.: 2086 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0559

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.0237

Gnomad SAS AF: 0.0394

Gnomad FIN AF: 0.00575

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0237

Gnomad OTH AF: 0.0948

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

GnomAD4 genome AF: 0.107 AC: 16256 AN: 152142 Hom.: 2099 Cov.: 32 AF XY: 0.103 AC XY: 7653 AN XY: 74394

African (AFR) AF: 0.310 AC: 12827 AN: 41440

American (AMR) AF: 0.0558 AC: 853 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0971 AC: 337 AN: 3470

East Asian (EAS) AF: 0.0240 AC: 124 AN: 5170

South Asian (SAS) AF: 0.0394 AC: 190 AN: 4824

European-Finnish (FIN) AF: 0.00575 AC: 61 AN: 10612

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0237 AC: 1612 AN: 68018

Other (OTH) AF: 0.0938 AC: 198 AN: 2110

Alfa AF: 0.0828 Hom.: 1665

Bravo AF: 0.119

Asia WGS AF: 0.0530 AC: 187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.45
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6099122; hg19: chr20-54953284;