Variant chr19-40233606-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.649

Variant links:

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]

AKT2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Effect	#exon/exons	MANE	Protein
AKT2	NM_001626.6 linkuse as main transcript	c.*266T>C	3_prime_UTR_variant	14/14	ENST00000392038.7	NP_001617.1
AKT2	NM_001243027.3 linkuse as main transcript	c.*266T>C	3_prime_UTR_variant	14/14		NP_001229956.1
AKT2	NM_001243028.3 linkuse as main transcript	c.*266T>C	3_prime_UTR_variant	13/13		NP_001229957.1
AKT2	NM_001330511.1 linkuse as main transcript	c.*266T>C	3_prime_UTR_variant	12/12		NP_001317440.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKT2	ENST00000392038.7 linkuse as main transcript	c.*266T>C	3_prime_UTR_variant	14/14	1	NM_001626.6	ENSP00000375892	P1	P31751-1
AKT2	ENST00000424901.5 linkuse as main transcript	c.*266T>C	3_prime_UTR_variant	13/13	5		ENSP00000399532		P31751-2
AKT2	ENST00000476266.5 linkuse as main transcript	n.2040T>C	non_coding_transcript_exon_variant	10/10	5
AKT2	ENST00000483166.5 linkuse as main transcript	n.3183T>C	non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.398

AC:

60365

AN:

151702

Hom.:

13469

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.487

AC XY:

153293

AN XY:

314560

show subpopulations

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.:

AF XY:

0.400

AC XY:

29640

AN XY:

74172

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over