rs749123022

Variant names:

• chr19-57231759-ACAGCCCAG-A
• rs749123022
• NM_001015878.2:c.94_101delAGCCCAGC

Your query was ambiguous. Multiple possible variants found:

• chr19-57231759-ACAGCCCAG-A
• chr19-57231759-ACAGCCCAG-ACAGCCCAGCAGCCCAG
• chr19-57231759-ACAGCCCAG-ACAGCCCAGCAGCCCAGCAGCCCAG

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001015878.2(AURKC):​c.94_101delAGCCCAGC​(p.Ser32HisfsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000205 in 1,613,434 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: AURKC NM_001015878.2 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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 6 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. Fraction of 0.899 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKC	NM_001015878.2	c.94_101delAGCCCAGC	p.Ser32HisfsTer8	frameshift_variant	Exon 2 of 7	ENST00000302804.12	NP_001015878.1
AURKC	NM_001015879.2	c.37_44delAGCCCAGC	p.Ser13HisfsTer8	frameshift_variant	Exon 2 of 7		NP_001015879.1
AURKC	XM_047439253.1	c.94_101delAGCCCAGC	p.Ser32HisfsTer8	frameshift_variant	Exon 2 of 5		XP_047295209.1
AURKC	NM_003160.3	c.-9_-2delAGCCCAGC		5_prime_UTR_variant	Exon 2 of 7		NP_003151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKC	ENST00000302804.12	c.94_101delAGCCCAGC	p.Ser32HisfsTer8	frameshift_variant	Exon 2 of 7	1	NM_001015878.2	ENSP00000302898.6

Frequencies

GnomAD3 genomes AF: 0.000139 AC: 21 AN: 151432 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000482

GnomAD3 exomes AF: 0.000148 AC: 37 AN: 250472 Hom.: 0 AF XY: 0.000155 AC XY: 21 AN XY: 135450

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000457

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000142

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000212 AC: 310 AN: 1461884 Hom.: 0 AF XY: 0.000223 AC XY: 162 AN XY: 727244

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000378

Gnomad4 SAS exome AF: 0.000614

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.000189

Gnomad4 OTH exome AF: 0.000298

GnomAD4 genome AF: 0.000139 AC: 21 AN: 151550 Hom.: 0 Cov.: 31 AF XY: 0.000122 AC XY: 9 AN XY: 74016

Gnomad4 AFR AF: 0.000218

Gnomad4 AMR AF: 0.000132

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.000477

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000125

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs749123022; hg19: chr19-57743127;