17-8207281-T-C

Position:

• chr17-8207281-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004217.4(AURKB):​c.293A>G​(p.Lys98Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AURKB NM_004217.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.82

Genes affected

AURKB (HGNC:11390): (aurora kinase B) This gene encodes a member of the aurora kinase subfamily of serine/threonine kinases. The genes encoding the other two members of this subfamily are located on chromosomes 19 and 20. These kinases participate in the regulation of alignment and segregation of chromosomes during mitosis and meiosis through association with microtubules. A pseudogene of this gene is located on chromosome 8. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2015]

AURKB (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1812244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AURKB	NM_004217.4	c.293A>G	p.Lys98Arg	missense_variant	5/9	ENST00000585124.6	NP_004208.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AURKB	ENST00000585124.6	c.293A>G	p.Lys98Arg	missense_variant	5/9	1	NM_004217.4	ENSP00000463999.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 15, 2024

The c.293A>G (p.K98R) alteration is located in exon 5 (coding exon 4) of the AURKB gene. This alteration results from a A to G substitution at nucleotide position 293, causing the lysine (K) at amino acid position 98 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.071	.;.;T;.;T;.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.037
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.18	T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.57	.;.;N;.;.;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.92	.;N;.;.;.;.;.
REVEL	Benign	0.045
Sift	Benign	0.38	.;T;.;.;.;.;.
Sift4G	Benign	0.37	T;T;T;.;.;T;.
Polyphen		0.095	.;.;B;.;.;.;.
Vest4		0.11
MutPred		0.33		.;.;Gain of MoRF binding (P = 0.0766);.;Gain of MoRF binding (P = 0.0766);.;.;
MVP		0.83
MPC		0.19
ClinPred		0.57	D
GERP RS		5.2
Varity_R		0.35
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr17-8110599;