19-57231125-AGGACGAGCAGGATT-A

Variant names:

• chr19-57231125-AGGACGAGCAGGATT-A
• rs58682946
• NM_001015878.2:c.-120_-107delCGAGCAGGATTGGA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001015878.2(AURKC):​c.-120_-107delCGAGCAGGATTGGA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 1,456,290 control chromosomes in the GnomAD database, including 509,731 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.76 (44830 hom., cov: 0)
  • Exomes 𝑓: 0.84 (464901 hom.)
• Consequence: AURKC NM_001015878.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.896
• Publications: 1 publications found

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]

AURKC Gene-Disease associations (from GenCC):

• spermatogenic failure 5

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 19-57231125-AGGACGAGCAGGATT-A is Benign according to our data. Variant chr19-57231125-AGGACGAGCAGGATT-A is described in ClinVar as [Benign]. Clinvar id is 1295147.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKC	NM_001015878.2	c.-120_-107delCGAGCAGGATTGGA		5_prime_UTR_variant	Exon 1 of 7	ENST00000302804.12	NP_001015878.1
AURKC	XM_047439253.1	c.-120_-107delCGAGCAGGATTGGA		5_prime_UTR_variant	Exon 1 of 5		XP_047295209.1
AURKC	NM_001015879.2	c.1+15_1+28delCGAGCAGGATTGGA		intron_variant	Intron 1 of 6		NP_001015879.1
AURKC	NM_003160.3	c.-45+10_-45+23delCGAGCAGGATTGGA		intron_variant	Intron 1 of 6		NP_003151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKC	ENST00000302804.12	c.-120_-107delCGAGCAGGATTGGA		5_prime_UTR_variant	Exon 1 of 7	1	NM_001015878.2	ENSP00000302898.6

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115317 AN: 151364 Hom.: 44821 Cov.: 0

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.745

GnomAD2 exomes AF: 0.824 AC: 107947 AN: 131070 AF XY: 0.831

Gnomad AFR exome AF: 0.550

Gnomad AMR exome AF: 0.842

Gnomad ASJ exome AF: 0.854

Gnomad EAS exome AF: 0.856

Gnomad FIN exome AF: 0.926

Gnomad NFE exome AF: 0.797

Gnomad OTH exome AF: 0.797

GnomAD4 exome AF: 0.835 AC: 1089902 AN: 1304810 Hom.: 464901 AF XY: 0.838 AC XY: 538365 AN XY: 642606

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.599 AC: 17429 AN: 29120

American (AMR) AF: 0.853 AC: 28298 AN: 33164

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 20475 AN: 23474

East Asian (EAS) AF: 0.842 AC: 29703 AN: 35288

South Asian (SAS) AF: 0.881 AC: 65806 AN: 74702

European-Finnish (FIN) AF: 0.901 AC: 43741 AN: 48536

Middle Eastern (MID) AF: 0.766 AC: 4148 AN: 5418

European-Non Finnish (NFE) AF: 0.835 AC: 835460 AN: 1000460

Other (OTH) AF: 0.821 AC: 44842 AN: 54648

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.762 AC: 115364 AN: 151480 Hom.: 44830 Cov.: 0 AF XY: 0.768 AC XY: 56818 AN XY: 74000

African (AFR) AF: 0.597 AC: 24644 AN: 41296

American (AMR) AF: 0.792 AC: 12076 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2960 AN: 3462

East Asian (EAS) AF: 0.847 AC: 4317 AN: 5096

South Asian (SAS) AF: 0.850 AC: 4087 AN: 4810

European-Finnish (FIN) AF: 0.906 AC: 9552 AN: 10544

Middle Eastern (MID) AF: 0.757 AC: 221 AN: 292

European-Non Finnish (NFE) AF: 0.815 AC: 55210 AN: 67722

Other (OTH) AF: 0.744 AC: 1566 AN: 2104

Alfa AF: 0.776 Hom.: 8074

Asia WGS AF: 0.806 AC: 2797 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 21, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.90
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs58682946; hg19: chr19-57742493; COSMIC: COSV104406875; COSMIC: COSV104406875;