rs35588791

Positions:

chr19-40257008-G-A

Variant summary

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

The NM_001626.6(AKT2):c.93C>T(p.Ser31Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,614,128 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 37 hom. )

Consequence

AKT2
NM_001626.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.00500

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:

AKT2 (HGNC:):

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=-0.52).

BP6

Variant 19-40257008-G-A is Benign according to our data. Variant chr19-40257008-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 434118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40257008-G-A is described in Lovd as [Likely_benign]. Variant chr19-40257008-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.005 with no splicing effect.

BS2

High AC in GnomAd4 at 446 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKT2	NM_001626.6 linkuse as main transcript	c.93C>T	p.Ser31Ser	synonymous_variant	3/14	ENST00000392038.7	NP_001617.1	P31751-1
AKT2	NM_001330511.1 linkuse as main transcript	c.93C>T	p.Ser31Ser	synonymous_variant	2/12		NP_001317440.1	P31751-2
AKT2	NM_001243027.3 linkuse as main transcript	c.-94C>T		5_prime_UTR_variant	3/14		NP_001229956.1	B4DG79
AKT2	NM_001243028.3 linkuse as main transcript	c.-94C>T		5_prime_UTR_variant	2/13		NP_001229957.1	B4DG79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKT2	ENST00000392038.7 linkuse as main transcript	c.93C>T	p.Ser31Ser	synonymous_variant	3/14	1	NM_001626.6	ENSP00000375892.2		P31751-1

Frequencies

GnomAD3 genomes

AF:

0.00294

AC:

447

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0103

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00444

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00357

AC:

898

AN:

251480

Hom.:

AF XY:

0.00413

AC XY:

562

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00188

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0114

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.00406

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00439

AC:

6413

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00457

AC XY:

3324

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0113

Gnomad4 FIN exome

AF:

0.000749

Gnomad4 NFE exome

AF:

0.00453

Gnomad4 OTH exome

AF:

0.00384

GnomAD4 genome

AF:

0.00293

AC:

446

AN:

152320

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

227

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0101

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00444

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00364

Hom.:

Bravo

AF:

0.00292

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00371

EpiControl

AF:

0.00445

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	AKT2: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jun 25, 2019	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Type 2 diabetes mellitus

Benign:1

Likely benign, criteria provided, single submitter

research

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Potent mutationsin AKT2 gene are associated with familial partial lipodystrophy and in terms of metabolic abnormality, can present with insulin resistance, hyperglycemia and Diabetes. In, silico analysis revealed that this particular rs35588791 is prevalent with Type 2 Diabetes -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.83

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