rs3730051

Positions:

• chr19-40238790-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000392038.7(AKT2):​c.708+115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,118,092 control chromosomes in the GnomAD database, including 37,613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4718 hom., cov: 31)
  • Exomes 𝑓: 0.26 (32895 hom.)
• Consequence: AKT2 ENST00000392038.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.78

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-40238790-T-C is Benign according to our data. Variant chr19-40238790-T-C is described in ClinVar as [Benign]. Clinvar id is 1233959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKT2	NM_001626.6	c.708+115A>G		intron_variant		ENST00000392038.7	NP_001617.1
AKT2	NM_001243027.3	c.522+115A>G		intron_variant			NP_001229956.1
AKT2	NM_001243028.3	c.522+115A>G		intron_variant			NP_001229957.1
AKT2	NM_001330511.1	c.708+115A>G		intron_variant			NP_001317440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKT2	ENST00000392038.7	c.708+115A>G		intron_variant		1	NM_001626.6	ENSP00000375892	P1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37228 AN: 151764 Hom.: 4722 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.258

GnomAD4 exome AF: 0.257 AC: 247838 AN: 966210 Hom.: 32895 AF XY: 0.255 AC XY: 127557 AN XY: 500892

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.360

Gnomad4 EAS exome AF: 0.317

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.312

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.245 AC: 37245 AN: 151882 Hom.: 4718 Cov.: 31 AF XY: 0.249 AC XY: 18496 AN XY: 74216

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.260

Alfa AF: 0.252 Hom.: 771

Bravo AF: 0.238

Asia WGS AF: 0.214 AC: 742 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.61

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: rs3730051; hg19: chr19-40744697; COSMIC: COSV60910946; COSMIC: COSV60910946;