chr19-57231300-G-GA

Position:

• chr19-57231300-G-GA

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The ENST00000302804.12(AURKC):​c.54dup​(p.Glu19ArgfsTer24) variant causes a frameshift 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 Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: AURKC ENST00000302804.12 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.00500

Genes affected

AURKC (HGNC:11391): (aurora kinase C) This gene encodes a member of the Aurora subfamily of serine/threonine protein kinases. The encoded protein is a chromosomal passenger protein that forms complexes with Aurora-B and inner centromere proteins and may play a role in organizing microtubules in relation to centrosome/spindle function during mitosis. This gene is overexpressed in several cancer cell lines, suggesting an involvement in oncogenic signal transduction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 5 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-57231300-G-GA is Pathogenic according to our data. Variant chr19-57231300-G-GA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1335371.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AURKC	NM_001015878.2	c.54dup	p.Glu19ArgfsTer24	frameshift_variant	1/7	ENST00000302804.12	NP_001015878.1
AURKC	XM_047439253.1	c.54dup	p.Glu19ArgfsTer24	frameshift_variant	1/5		XP_047295209.1
AURKC	NM_001015879.2	c.1+188dup		intron_variant			NP_001015879.1
AURKC	NM_003160.3	c.-45+183dup		intron_variant			NP_003151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AURKC	ENST00000302804.12	c.54dup	p.Glu19ArgfsTer24	frameshift_variant	1/7	1	NM_001015878.2	ENSP00000302898	A2
AURKC	ENST00000599062.5	c.54dup	p.Glu19ArgfsTer21	frameshift_variant	1/7	1		ENSP00000469983	P2
AURKC	ENST00000415300.6	c.1+188dup		intron_variant		1		ENSP00000407162
AURKC	ENST00000601799.5	c.54dup	p.Glu19ArgfsTer3	frameshift_variant, NMD_transcript_variant	1/6	3		ENSP00000468918

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 30

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs1568483365; hg19: chr19-57742668;