chr20-56370155-T-G

Variant names:

• chr20-56370155-T-G
• rs34361943
• NM_198437.3:c.*3A>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_198437.3(AURKA):​c.*3A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 1,612,342 control chromosomes in the GnomAD database, including 484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.016 (39 hom., cov: 32)
  • Exomes 𝑓: 0.022 (445 hom.)
• Consequence: AURKA NM_198437.3 3_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.29
• Publications: 6 publications found

Genes affected

AURKA (HGNC:11393): (aurora kinase A) The protein encoded by this gene is a cell cycle-regulated kinase that appears to be involved in microtubule formation and/or stabilization at the spindle pole during chromosome segregation. The encoded protein is found at the centrosome in interphase cells and at the spindle poles in mitosis. This gene may play a role in tumor development and progression. A processed pseudogene of this gene has been found on chromosome 1, and an unprocessed pseudogene has been found on chromosome 10. Multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

AURKA Gene-Disease associations (from GenCC):

• breast cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 20-56370155-T-G is Benign according to our data. Variant chr20-56370155-T-G is described in ClinVar as Benign. ClinVar VariationId is 3037417.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0163 (2485/152334) while in subpopulation NFE AF = 0.0214 (1454/68034). AF 95% confidence interval is 0.0205. There are 39 homozygotes in GnomAd4. There are 1337 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2485 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198437.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	NM_198437.3	MANE Select	c.*3A>C		3_prime_UTR	Exon 9 of 9	NP_940839.1	O14965
	AURKA	NM_001424418.1		c.*3A>C		3_prime_UTR	Exon 11 of 11	NP_001411347.1
	AURKA	NM_001424419.1		c.*3A>C		3_prime_UTR	Exon 11 of 11	NP_001411348.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	ENST00000395915.8	TSL:1 MANE Select	c.*3A>C		3_prime_UTR	Exon 9 of 9	ENSP00000379251.3	O14965
	AURKA	ENST00000312783.10	TSL:1	c.*3A>C		3_prime_UTR	Exon 10 of 10	ENSP00000321591.6	O14965
	AURKA	ENST00000347343.6	TSL:1	c.*3A>C		3_prime_UTR	Exon 9 of 9	ENSP00000216911.2	O14965

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2485 AN: 152216 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.00432

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.00851

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0564

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0214

Gnomad OTH AF: 0.0143

GnomAD2 exomes AF: 0.0187 AC: 4694 AN: 251408 AF XY: 0.0193

Gnomad AFR exome AF: 0.00394

Gnomad AMR exome AF: 0.00838

Gnomad ASJ exome AF: 0.00377

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0533

Gnomad NFE exome AF: 0.0230

Gnomad OTH exome AF: 0.0182

GnomAD4 exome AF: 0.0216 AC: 31489 AN: 1460008 Hom.: 445 Cov.: 32 AF XY: 0.0213 AC XY: 15503 AN XY: 726308

African (AFR) AF: 0.00287 AC: 96 AN: 33420

American (AMR) AF: 0.00847 AC: 379 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00390 AC: 102 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0136 AC: 1171 AN: 86174

European-Finnish (FIN) AF: 0.0498 AC: 2662 AN: 53416

Middle Eastern (MID) AF: 0.0100 AC: 43 AN: 4282

European-Non Finnish (NFE) AF: 0.0232 AC: 25812 AN: 1111924

Other (OTH) AF: 0.0203 AC: 1224 AN: 60238

GnomAD4 genome AF: 0.0163 AC: 2485 AN: 152334 Hom.: 39 Cov.: 32 AF XY: 0.0179 AC XY: 1337 AN XY: 74490

African (AFR) AF: 0.00430 AC: 179 AN: 41584

American (AMR) AF: 0.00849 AC: 130 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0120 AC: 58 AN: 4826

European-Finnish (FIN) AF: 0.0564 AC: 598 AN: 10610

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0214 AC: 1454 AN: 68034

Other (OTH) AF: 0.0142 AC: 30 AN: 2116

Alfa AF: 0.0174 Hom.: 13

Bravo AF: 0.0120

Asia WGS AF: 0.00549 AC: 20 AN: 3478

EpiCase AF: 0.0206

EpiControl AF: 0.0213

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	AURKA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.7
DANN	Benign	0.80
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs34361943; hg19: chr20-54945211; COSMIC: COSV57167435;