Variant chr19-40233814-G-T 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.*58C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,573,762 control chromosomes in the GnomAD database, including 180,197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 13281 hom., cov: 31)

Exomes 𝑓: 0.48 ( 166916 hom. )

Consequence

AKT2
NM_001626.6 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.362

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=-0.85).

BP6

Variant 19-40233814-G-T is Benign according to our data. Variant chr19-40233814-G-T is described in ClinVar as [Benign]. Clinvar id is 1224269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
AKT2	NM_001626.6 linkuse as main transcript	c.*58C>A	3_prime_UTR_variant	14/14	ENST00000392038.7
AKT2	NM_001243027.3 linkuse as main transcript	c.*58C>A	3_prime_UTR_variant	14/14
AKT2	NM_001243028.3 linkuse as main transcript	c.*58C>A	3_prime_UTR_variant	13/13
AKT2	NM_001330511.1 linkuse as main transcript	c.*58C>A	3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKT2	ENST00000392038.7 linkuse as main transcript	c.*58C>A		3_prime_UTR_variant	14/14	1	NM_001626.6	P1	P31751-1

Frequencies

GnomAD3 genomes

AF:

0.395

AC:

59904

AN:

151718

Hom.:

13281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.375

Gnomad AMR

AF:

0.508

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.483

Gnomad SAS

AF:

0.591

Gnomad FIN

AF:

0.430

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.474

Gnomad OTH

AF:

0.401

GnomAD4 exome

AF:

0.480

AC:

682051

AN:

1421932

Hom.:

166916

Cov.:

AF XY:

0.482

AC XY:

341182

AN XY:

707504

show subpopulations

Gnomad4 AFR exome

AF:

0.162

Gnomad4 AMR exome

AF:

0.595

Gnomad4 ASJ exome

AF:

0.377

Gnomad4 EAS exome

AF:

0.460

Gnomad4 SAS exome

AF:

0.589

Gnomad4 FIN exome

AF:

0.445

Gnomad4 NFE exome

AF:

0.482

Gnomad4 OTH exome

AF:

0.466

GnomAD4 genome

AF:

0.395

AC:

59910

AN:

151830

Hom.:

13281

Cov.:

AF XY:

0.396

AC XY:

29408

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.180

Gnomad4 AMR

AF:

0.508

Gnomad4 ASJ

AF:

0.389

Gnomad4 EAS

AF:

0.483

Gnomad4 SAS

AF:

0.590

Gnomad4 FIN

AF:

0.430

Gnomad4 NFE

AF:

0.474

Gnomad4 OTH

AF:

0.402

Alfa

AF:

0.453

Hom.:

14389

Bravo

AF:

0.391

Asia WGS

AF:

0.518

AC:

1802

AN:

3476

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	This variant is associated with the following publications: (PMID: 33768461) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.3

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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