rs892119

Positions:

• chr19-40254165-C-T

Variant summary

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

The NM_001626.6(AKT2):​c.287+993G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 132,644 control chromosomes in the GnomAD database, including 2,251 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 0.19 (2251 hom., cov: 30)
• Consequence: AKT2 NM_001626.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83

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]

LOC107985289 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKT2	NM_001626.6	c.287+993G>A		intron_variant		ENST00000392038.7
LOC107985289	XR_001753939.2	n.163G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKT2	ENST00000392038.7	c.287+993G>A		intron_variant		1	NM_001626.6	P1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 25277 AN: 132520 Hom.: 2243 Cov.: 30

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.191 AC: 25316 AN: 132644 Hom.: 2251 Cov.: 30 AF XY: 0.191 AC XY: 12330 AN XY: 64566

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.185

Alfa AF: 0.156 Hom.: 934

Bravo AF: 0.164

Asia WGS AF: 0.121 AC: 419 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.88

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: rs892119; hg19: chr19-40760072;