rs11671439

chr19-40272270-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.-84-6919A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,230 control chromosomes in the GnomAD database, including 1,584 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 0.12 (1584 hom., cov: 32)
• Consequence: AKT2 NM_001626.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.675

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKT2	NM_001626.6	c.-84-6919A>G		intron_variant		ENST00000392038.7
AKT2	NM_001243027.3	c.-233-6919A>G		intron_variant
AKT2	NM_001243028.3	c.-141+12911A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKT2	ENST00000392038.7	c.-84-6919A>G		intron_variant		1	NM_001626.6	P1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18238 AN: 152112 Hom.: 1583 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.0762

Gnomad ASJ AF: 0.0807

Gnomad EAS AF: 0.0535

Gnomad SAS AF: 0.0649

Gnomad FIN AF: 0.0544

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0778

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.120 AC: 18259 AN: 152230 Hom.: 1584 Cov.: 32 AF XY: 0.118 AC XY: 8769 AN XY: 74456

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.0761

Gnomad4 ASJ AF: 0.0807

Gnomad4 EAS AF: 0.0529

Gnomad4 SAS AF: 0.0650

Gnomad4 FIN AF: 0.0544

Gnomad4 NFE AF: 0.0778

Gnomad4 OTH AF: 0.117

Alfa AF: 0.103 Hom.: 185

Bravo AF: 0.126

Asia WGS AF: 0.0770 AC: 267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.2
Dann	Benign	0.38

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: rs11671439; hg19: chr19-40778177;