17-8205230-G-A

Position:

• chr17-8205230-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_004217.4(AURKB):​c.847C>T​(p.Arg283Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,090 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AURKB NM_004217.4 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.350

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-8205230-G-A is Pathogenic according to our data. Variant chr17-8205230-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 638622.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AURKB	NM_004217.4	c.847C>T	p.Arg283Cys	missense_variant	8/9	ENST00000585124.6	NP_004208.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AURKB	ENST00000585124.6	c.847C>T	p.Arg283Cys	missense_variant	8/9	1	NM_004217.4	ENSP00000463999.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461090 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726744

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

NK-cell enteropathy Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Xiao lab, Department of Pathology, Memorial Sloan Kettering Cancer Center

Jul 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.29	.;.;T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.69	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.2	.;.;M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-6.0	D;D;.;.
REVEL	Uncertain	0.31
Sift	Uncertain	0.026	D;D;.;.
Sift4G	Uncertain	0.015	D;D;D;D
Polyphen		0.96	.;.;D;.
Vest4		0.63
MutPred		0.60		.;.;Loss of disorder (P = 0.0175);.;
MVP		0.61
MPC		0.77
ClinPred		0.99	D
GERP RS		-0.96
Varity_R		0.49
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1597343914; hg19: chr17-8108548; COSMIC: COSV60245973; COSMIC: COSV60245973;