19-40246116-C-G

Position:

• chr19-40246116-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001626.6(AKT2):​c.288-3429G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 149,930 control chromosomes in the GnomAD database, including 39,883 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.73 (39883 hom., cov: 28)
• Consequence: AKT2 NM_001626.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKT2	NM_001626.6	c.288-3429G>C		intron_variant		ENST00000392038.7	NP_001617.1
AKT2	NM_001330511.1	c.288-3429G>C		intron_variant			NP_001317440.1
AKT2	NM_001243027.3	c.102-3429G>C		intron_variant			NP_001229956.1
AKT2	NM_001243028.3	c.102-3429G>C		intron_variant			NP_001229957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKT2	ENST00000392038.7	c.288-3429G>C		intron_variant		1	NM_001626.6	ENSP00000375892.2

Frequencies

GnomAD3 genomes AF: 0.727 AC: 109018 AN: 149858 Hom.: 39864 Cov.: 28

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.718

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.728 AC: 109080 AN: 149930 Hom.: 39883 Cov.: 28 AF XY: 0.724 AC XY: 52878 AN XY: 73002

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.717

Alfa AF: 0.611 Hom.: 1577

Bravo AF: 0.736

Asia WGS AF: 0.732 AC: 2548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.20
DANN	Benign	0.31

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

Other links and lift over

dbSNP: rs8100018; hg19: chr19-40752023;