20-56370285-C-A

Position:

• chr20-56370285-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000395915.8(AURKA):​c.1085G>T​(p.Arg362Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AURKA ENST00000395915.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.24

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AURKA	NM_198437.3	c.1085G>T	p.Arg362Ile	missense_variant	9/9	ENST00000395915.8	NP_940839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AURKA	ENST00000395915.8	c.1085G>T	p.Arg362Ile	missense_variant	9/9	1	NM_198437.3	ENSP00000379251	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Colorectal cancer Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Mar 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	0.98
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Uncertain	0.092	D
MetaRNN	Uncertain	0.51	D;D;D;D;D;D;D
MetaSVM	Benign	-0.48	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.3	D;D;D;D;D;D;D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D;D;D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D;D;D
Vest4		0.46
MutPred		0.58		Loss of disorder (P = 0.039);Loss of disorder (P = 0.039);Loss of disorder (P = 0.039);Loss of disorder (P = 0.039);Loss of disorder (P = 0.039);Loss of disorder (P = 0.039);Loss of disorder (P = 0.039);
MVP		0.61
ClinPred		0.97	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.58

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-54945341;