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GeneBe

19-40235025-C-T

Variant summary

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

The ENST00000579047.5(AKT2):c.1200G>A(p.Pro400=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000413 in 1,608,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00041 ( 0 hom. )

Consequence

AKT2
ENST00000579047.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.75
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-40235025-C-T is Benign according to our data. Variant chr19-40235025-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1598854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.75 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 61 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AKT2NM_001626.6 linkuse as main transcriptc.1366+20G>A intron_variant ENST00000392038.7
AKT2NM_001243027.3 linkuse as main transcriptc.1180+20G>A intron_variant
AKT2NM_001243028.3 linkuse as main transcriptc.1180+20G>A intron_variant
AKT2NM_001330511.1 linkuse as main transcriptc.1237+20G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AKT2ENST00000392038.7 linkuse as main transcriptc.1366+20G>A intron_variant 1 NM_001626.6 P1P31751-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000401
AC:
61
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000764
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000403
AC:
101
AN:
250566
Hom.:
1
AF XY:
0.000450
AC XY:
61
AN XY:
135654
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000465
Gnomad NFE exome
AF:
0.000724
Gnomad OTH exome
AF:
0.000817
GnomAD4 exome
AF:
0.000414
AC:
603
AN:
1456422
Hom.:
0
Cov.:
30
AF XY:
0.000451
AC XY:
327
AN XY:
724880
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.000470
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000500
Gnomad4 OTH exome
AF:
0.000249
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000400
AC:
61
AN:
152312
Hom.:
0
Cov.:
32
AF XY:
0.000336
AC XY:
25
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000764
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000466
Hom.:
0
Bravo
AF:
0.000438

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Type 2 diabetes mellitus;C3278384:Hypoinsulinemic hypoglycemia and body hemihypertrophy Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 08, 2024- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2023AKT2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
Cadd
Benign
0.012
Dann
Benign
0.76
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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.

Other links and lift over

dbSNP: rs375549081; hg19: chr19-40740932; API