Variant 19-40235955-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001626.6(AKT2):c.1110G>T(p.Pro370=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00284 in 1,613,886 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 17 hom. )

Consequence

AKT2
NM_001626.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.88

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 19-40235955-C-A is Benign according to our data. Variant chr19-40235955-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 466265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40235955-C-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-3.88 with no splicing effect.

BS2

High AC in GnomAd4 at 457 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AKT2	NM_001626.6 linkuse as main transcript	c.1110G>T	p.Pro370=	synonymous_variant	11/14	ENST00000392038.7	NP_001617.1
AKT2	NM_001330511.1 linkuse as main transcript	c.981G>T	p.Pro327=	synonymous_variant	9/12		NP_001317440.1
AKT2	NM_001243027.3 linkuse as main transcript	c.924G>T	p.Pro308=	synonymous_variant	11/14		NP_001229956.1
AKT2	NM_001243028.3 linkuse as main transcript	c.924G>T	p.Pro308=	synonymous_variant	10/13		NP_001229957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKT2	ENST00000392038.7 linkuse as main transcript	c.1110G>T	p.Pro370=	synonymous_variant	11/14	1	NM_001626.6	ENSP00000375892	P1	P31751-1

Frequencies

GnomAD3 genomes

AF:

0.00300

AC:

457

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0228

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00257

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00342

AC:

858

AN:

250904

Hom.:

AF XY:

0.00323

AC XY:

439

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.000555

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0216

Gnomad NFE exome

AF:

0.00303

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00282

AC:

4120

AN:

1461658

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

1985

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000649

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0213

Gnomad4 NFE exome

AF:

0.00253

Gnomad4 OTH exome

AF:

0.00210

GnomAD4 genome

AF:

0.00300

AC:

457

AN:

152228

Hom.:

Cov.:

AF XY:

0.00387

AC XY:

288

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0228

Gnomad4 NFE

AF:

0.00257

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00125

Hom.:

Bravo

AF:

0.00148

EpiCase

AF:

0.00245

EpiControl

AF:

0.00190

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	AKT2: BP4, BP7 -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Type 2 diabetes mellitus;C3278384:Hypoinsulinemic hypoglycemia and body hemihypertrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.48

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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