19-40272959-T-C

Position:

• chr19-40272959-T-C

Variant summary

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

The NM_001626.6(AKT2):​c.-84-7608A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,038 control chromosomes in the GnomAD database, including 40,425 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 (40425 hom., cov: 31)
• Consequence: AKT2 NM_001626.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.33

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=-0.93).
• 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.-84-7608A>G		intron_variant		ENST00000392038.7	NP_001617.1
AKT2	NM_001243027.3	c.-233-7608A>G		intron_variant			NP_001229956.1
AKT2	NM_001243028.3	c.-141+12222A>G		intron_variant			NP_001229957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKT2	ENST00000392038.7	c.-84-7608A>G		intron_variant		1	NM_001626.6	ENSP00000375892.2

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110512 AN: 151920 Hom.: 40394 Cov.: 31

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.718

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

GnomAD4 genome AF: 0.727 AC: 110606 AN: 152038 Hom.: 40425 Cov.: 31 AF XY: 0.724 AC XY: 53830 AN XY: 74300

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.717

Alfa AF: 0.667 Hom.: 3465

Bravo AF: 0.735

Asia WGS AF: 0.736 AC: 2559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.94
DANN	Benign	0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs969531; hg19: chr19-40778866;