chr19-40235026-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000579047.5(AKT2):​c.1199C>T​(p.Pro400Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000597 in 1,608,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P400P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

AKT2
ENST00000579047.5 missense

Scores

1
8

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.835
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 -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.019796968).
BP6
Variant 19-40235026-G-A is Benign according to our data. Variant chr19-40235026-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2950331.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 48 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AKT2NM_001626.6 linkuse as main transcriptc.1366+19C>T intron_variant ENST00000392038.7
AKT2NM_001243027.3 linkuse as main transcriptc.1180+19C>T intron_variant
AKT2NM_001243028.3 linkuse as main transcriptc.1180+19C>T intron_variant
AKT2NM_001330511.1 linkuse as main transcriptc.1237+19C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AKT2ENST00000392038.7 linkuse as main transcriptc.1366+19C>T intron_variant 1 NM_001626.6 P1P31751-1

Frequencies

GnomAD3 genomes
AF:
0.000322
AC:
49
AN:
152192
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000893
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000720
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000104
AC:
26
AN:
250662
Hom.:
0
AF XY:
0.000118
AC XY:
16
AN XY:
135678
show subpopulations
Gnomad AFR exome
AF:
0.000741
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000294
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000330
AC:
48
AN:
1456314
Hom.:
0
Cov.:
30
AF XY:
0.0000400
AC XY:
29
AN XY:
724872
show subpopulations
Gnomad4 AFR exome
AF:
0.000389
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000162
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000452
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
AF:
0.000315
AC:
48
AN:
152310
Hom.:
0
Cov.:
32
AF XY:
0.000322
AC XY:
24
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.000866
Gnomad4 AMR
AF:
0.000719
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000336
ESP6500AA
AF:
0.00114
AC:
5
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000124
AC:
15

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Type 2 diabetes mellitus;C3278384:Hypoinsulinemic hypoglycemia and body hemihypertrophy Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 26, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
0.12
DANN
Benign
0.75
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.0020
T
MetaRNN
Benign
0.020
T
MutationTaster
Benign
1.0
N;N;N
Sift4G
Uncertain
0.034
D
Vest4
0.095
MVP
0.83
GERP RS
-0.13
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: rs148795214; hg19: chr19-40740933; COSMIC: COSV104601683; COSMIC: COSV104601683; API