17-8206543-C-G

Position:

• chr17-8206543-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP3 BP4_Moderate BP6_Very_Strong BS2

The NM_004217.4(AURKB):​c.634G>C​(p.Gly212Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,614,192 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00098 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (3 hom.)
• Consequence: AURKB NM_004217.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.89

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 Benign. Variant got -13 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Cadd, Eigen, FATHMM_MKL, phyloP100way_vertebrate, PrimateAI, PROVEAN [when max_spliceai, M_CAP, MetaRNN, MutationTaster was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=0.24397597).
• BP6: Variant 17-8206543-C-G is Benign according to our data. Variant chr17-8206543-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 931197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 150 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AURKB	NM_004217.4	c.634G>C	p.Gly212Arg	missense_variant	7/9	ENST00000585124.6	NP_004208.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AURKB	ENST00000585124.6	c.634G>C	p.Gly212Arg	missense_variant	7/9	1	NM_004217.4	ENSP00000463999.1

Frequencies

GnomAD3 genomes AF: 0.000992 AC: 151 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00147

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.000958 AC: 241 AN: 251450 Hom.: 1 AF XY: 0.000957 AC XY: 130 AN XY: 135910

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00144

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00136

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00129 AC: 1890 AN: 1461886 Hom.: 3 Cov.: 31 AF XY: 0.00130 AC XY: 946 AN XY: 727246

Gnomad4 AFR exome AF: 0.000568

Gnomad4 AMR exome AF: 0.000894

Gnomad4 ASJ exome AF: 0.000306

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00144

Gnomad4 FIN exome AF: 0.000356

Gnomad4 NFE exome AF: 0.00146

Gnomad4 OTH exome AF: 0.000944

GnomAD4 genome AF: 0.000985 AC: 150 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.000967 AC XY: 72 AN XY: 74468

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00147

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00106 Hom.: 1

Bravo AF: 0.000903

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.000815 AC: 99

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00142

EpiControl AF: 0.00113

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Centre for Mendelian Genomics, University Medical Centre Ljubljana	Oct 26, 2018	This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2,PP3. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.36	.;.;T;.;.;T;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.24	T;T;T;T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	.;.;M;.;.;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-7.4	.;D;.;.;.;.;.
REVEL	Uncertain	0.51
Sift	Uncertain	0.0070	.;D;.;.;.;.;.
Sift4G	Uncertain	0.010	D;D;D;D;.;.;D
Polyphen		0.94	.;.;P;.;.;.;.
Vest4		0.88
MutPred		0.67		.;.;Loss of ubiquitination at K211 (P = 0.0455);.;.;Loss of ubiquitination at K211 (P = 0.0455);.;
MVP		0.95
MPC		0.83
ClinPred		0.093	T
GERP RS		5.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.82
gMVP		0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs149651741; hg19: chr17-8109861; COSMIC: COSV104412340; COSMIC: COSV104412340;