rs3730050

Positions:

• chr19-40265075-T-C

Variant summary

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

The NM_001626.6(AKT2):​c.46+147A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 1,193,186 control chromosomes in the GnomAD database, including 302,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (40491 hom., cov: 32)
  • Exomes 𝑓: 0.71 (262233 hom.)
• Consequence: AKT2 NM_001626.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.11

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=-0.94).
• BP6: Variant 19-40265075-T-C is Benign according to our data. Variant chr19-40265075-T-C is described in ClinVar as [Benign]. Clinvar id is 1182081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKT2	NM_001626.6	c.46+147A>G		intron_variant		ENST00000392038.7	NP_001617.1
AKT2	NM_001243027.3	c.-141+184A>G		intron_variant			NP_001229956.1
AKT2	NM_001243028.3	c.-140-8021A>G		intron_variant			NP_001229957.1
AKT2	NM_001330511.1	c.46+147A>G		intron_variant			NP_001317440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKT2	ENST00000392038.7	c.46+147A>G		intron_variant		1	NM_001626.6	ENSP00000375892	P1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110616 AN: 152000 Hom.: 40459 Cov.: 32

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.717

GnomAD4 exome AF: 0.708 AC: 737269 AN: 1041068 Hom.: 262233 AF XY: 0.709 AC XY: 372646 AN XY: 525516

Gnomad4 AFR exome AF: 0.798

Gnomad4 AMR exome AF: 0.759

Gnomad4 ASJ exome AF: 0.624

Gnomad4 EAS exome AF: 0.649

Gnomad4 SAS exome AF: 0.765

Gnomad4 FIN exome AF: 0.669

Gnomad4 NFE exome AF: 0.704

Gnomad4 OTH exome AF: 0.716

GnomAD4 genome AF: 0.728 AC: 110712 AN: 152118 Hom.: 40491 Cov.: 32 AF XY: 0.725 AC XY: 53884 AN XY: 74352

Gnomad4 AFR AF: 0.795

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.654

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.716

Alfa AF: 0.710 Hom.: 17467

Bravo AF: 0.735

Asia WGS AF: 0.736 AC: 2561 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	-0.94
CADD	Benign	0.0090
DANN	Benign	0.21

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: rs3730050; hg19: chr19-40770982;