chr19-40235151-C-T

Variant summary

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

The NM_001626.6(AKT2):​c.1264-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,613,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

AKT2
NM_001626.6 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.00004806
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.58
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 (BayesDel_noAF=-0.58).
BP6
Variant 19-40235151-C-T is Benign according to our data. Variant chr19-40235151-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2940438.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 48 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AKT2NM_001626.6 linkuse as main transcriptc.1264-4G>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000392038.7
AKT2NM_001243027.3 linkuse as main transcriptc.1078-4G>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
AKT2NM_001243028.3 linkuse as main transcriptc.1078-4G>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
AKT2NM_001330511.1 linkuse as main transcriptc.1135-4G>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AKT2ENST00000392038.7 linkuse as main transcriptc.1264-4G>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_001626.6 P1P31751-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151954
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000557
AC:
14
AN:
251376
Hom.:
0
AF XY:
0.0000441
AC XY:
6
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000328
AC:
48
AN:
1461846
Hom.:
0
Cov.:
31
AF XY:
0.0000371
AC XY:
27
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000198
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151954
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74210
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

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 testingInvitaeNov 12, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
CADD
Benign
9.4
DANN
Benign
0.81
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000048
dbscSNV1_RF
Benign
0.0060
SpliceAI score (max)
0.12
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: rs763704160; hg19: chr19-40741058; API