rs33933140

chr19-40233606-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001626.6(AKT2):c.*266T>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 0.465 in 726,250 control chromosomes in the GnomAD database, including 82,696 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (13469 hom., cov: 31)
  • Exomes 𝑓: 0.48 (69227 hom.)
• Consequence: AKT2 NM_001626.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.649

Genes affected

AKT2 (HGNC:392): (AKT serine/threonine kinase 2) This gene is a putative oncogene encoding a protein belonging to a subfamily of serine/threonine kinases containing SH2-like (Src homology 2-like) domains, which is involved in signaling pathways. The gene serves as an oncogene in the tumorigenesis of cancer cells For example, its overexpression contributes to the malignant phenotype of a subset of human ductal pancreatic cancers. The encoded protein is a general protein kinase capable of phophorylating several known proteins, and has also been implicated in insulin signaling. [provided by RefSeq, Nov 2019]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-40233606-A-G is Benign according to our data. Variant chr19-40233606-A-G is described in ClinVar as [Benign]. Clinvar id is 1182244.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-40233606-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKT2	NM_001626.6	c.*266T>C		3_prime_UTR_variant	14/14	ENST00000392038.7
AKT2	NM_001243027.3	c.*266T>C		3_prime_UTR_variant	14/14
AKT2	NM_001243028.3	c.*266T>C		3_prime_UTR_variant	13/13
AKT2	NM_001330511.1	c.*266T>C		3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKT2	ENST00000392038.7	c.*266T>C		3_prime_UTR_variant	14/14	1	NM_001626.6	P1
AKT2	ENST00000424901.5	c.*266T>C		3_prime_UTR_variant	13/13	5
AKT2	ENST00000476266.5	n.2040T>C		non_coding_transcript_exon_variant	10/10	5
AKT2	ENST00000483166.5	n.3183T>C		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60365 AN: 151702 Hom.: 13469 Cov.: 31

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.409

GnomAD3 exomes AF: 0.490 AC: 113125 AN: 231026 Hom.: 29069 AF XY: 0.492 AC XY: 62813 AN XY: 127578

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.603

Gnomad ASJ exome AF: 0.377

Gnomad EAS exome AF: 0.527

Gnomad SAS exome AF: 0.594

Gnomad FIN exome AF: 0.446

Gnomad NFE exome AF: 0.474

Gnomad OTH exome AF: 0.482

GnomAD4 exome AF: 0.482 AC: 277079 AN: 574430 Hom.: 69227 Cov.: 2 AF XY: 0.487 AC XY: 153293 AN XY: 314560

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.598

Gnomad4 ASJ exome AF: 0.378

Gnomad4 EAS exome AF: 0.473

Gnomad4 SAS exome AF: 0.591

Gnomad4 FIN exome AF: 0.446

Gnomad4 NFE exome AF: 0.474

Gnomad4 OTH exome AF: 0.466

GnomAD4 genome AF: 0.398 AC: 60374 AN: 151820 Hom.: 13469 Cov.: 31 AF XY: 0.400 AC XY: 29640 AN XY: 74172

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.410

Alfa AF: 0.454 Hom.: 6549

Bravo AF: 0.393

Asia WGS AF: 0.535 AC: 1859 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	9.0
Dann	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs33933140; hg19: chr19-40739513; COSMIC: COSV60908566; COSMIC: COSV60908566;