Variant chr19-40233863-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001626.6(AKT2):c.*9C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00971 in 1,610,172 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0098 ( 107 hom. )

Consequence

AKT2
NM_001626.6 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0460

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 19-40233863-G-A is Benign according to our data. Variant chr19-40233863-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1338691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0088 (1340/152352) while in subpopulation AMR AF= 0.0178 (273/15310). AF 95% confidence interval is 0.0161. There are 8 homozygotes in gnomad4. There are 630 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1340 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
AKT2	NM_001626.6 linkuse as main transcript	c.*9C>T	3_prime_UTR_variant	14/14	ENST00000392038.7
AKT2	NM_001243027.3 linkuse as main transcript	c.*9C>T	3_prime_UTR_variant	14/14
AKT2	NM_001243028.3 linkuse as main transcript	c.*9C>T	3_prime_UTR_variant	13/13
AKT2	NM_001330511.1 linkuse as main transcript	c.*9C>T	3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKT2	ENST00000392038.7 linkuse as main transcript	c.*9C>T		3_prime_UTR_variant	14/14	1	NM_001626.6	P1	P31751-1

Frequencies

GnomAD3 genomes

AF:

0.00881

AC:

1341

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0179

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.0119

GnomAD3 exomes

AF:

0.00864

AC:

2120

AN:

245300

Hom.:

AF XY:

0.00921

AC XY:

1227

AN XY:

133188

show subpopulations

Gnomad AFR exome

AF:

0.00173

Gnomad AMR exome

AF:

0.00953

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00415

Gnomad FIN exome

AF:

0.00203

Gnomad NFE exome

AF:

0.0126

Gnomad OTH exome

AF:

0.0129

GnomAD4 exome

AF:

0.00980

AC:

14287

AN:

1457820

Hom.:

107

Cov.:

AF XY:

0.00989

AC XY:

7176

AN XY:

725386

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.0124

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00525

Gnomad4 FIN exome

AF:

0.00203

Gnomad4 NFE exome

AF:

0.0109

Gnomad4 OTH exome

AF:

0.0105

GnomAD4 genome

AF:

0.00880

AC:

1340

AN:

152352

Hom.:

Cov.:

AF XY:

0.00846

AC XY:

630

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00274

Gnomad4 AMR

AF:

0.0178

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.0101

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 30, 2021

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.5

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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