rs7254617

Variant names:

• chr19-40285605-G-A
• rs7254617
• ENST00000391844.8:n.-555C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-40285605-G-A
• chr19-40285605-G-C
• chr19-40285605-G-T

Variant summary

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

The ENST00000578123.5(AKT2):​c.-242C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 357,842 control chromosomes in the GnomAD database, including 7,394 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 0.22 (4355 hom., cov: 31)
  • Exomes 𝑓: 0.17 (3039 hom.)
• Consequence: AKT2 ENST00000578123.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.944

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKT2	ENST00000391844.8	n.-555C>T		upstream_gene_variant		1		ENSP00000375719.4
AKT2	ENST00000424901.5	c.-509C>T		upstream_gene_variant		5		ENSP00000399532.2
AKT2	ENST00000578123.5	c.-242C>T		upstream_gene_variant		4		ENSP00000462022.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32900 AN: 151924 Hom.: 4338 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.200

GnomAD4 exome AF: 0.167 AC: 34289 AN: 205800 Hom.: 3039 AF XY: 0.166 AC XY: 17355 AN XY: 104824

Gnomad4 AFR exome AF: 0.366

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.217 AC: 32957 AN: 152042 Hom.: 4355 Cov.: 31 AF XY: 0.214 AC XY: 15936 AN XY: 74320

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.199

Alfa AF: 0.119 Hom.: 259

Bravo AF: 0.221

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.50
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7254617; hg19: chr19-40791512;