chr19-40236198-T-C

Position:

• chr19-40236198-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.960+59A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,612,974 control chromosomes in the GnomAD database, including 22,614 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3860 hom., cov: 32)
  • Exomes 𝑓: 0.16 (18754 hom.)
• Consequence: AKT2 NM_001626.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.122

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=-0.8).
• BP6: Variant 19-40236198-T-C is Benign according to our data. Variant chr19-40236198-T-C is described in ClinVar as [Benign]. Clinvar id is 1238745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKT2	NM_001626.6	c.960+59A>G		intron_variant		ENST00000392038.7
AKT2	NM_001243027.3	c.774+59A>G		intron_variant
AKT2	NM_001243028.3	c.774+59A>G		intron_variant
AKT2	NM_001330511.1	c.832-94A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKT2	ENST00000392038.7	c.960+59A>G		intron_variant		1	NM_001626.6	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31345 AN: 151726 Hom.: 3848 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.155 AC: 226558 AN: 1461130 Hom.: 18754 Cov.: 35 AF XY: 0.153 AC XY: 111448 AN XY: 726844

Gnomad4 AFR exome AF: 0.341

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.207 AC: 31395 AN: 151844 Hom.: 3860 Cov.: 32 AF XY: 0.204 AC XY: 15173 AN XY: 74224

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.192

Alfa AF: 0.172 Hom.: 931

Bravo AF: 0.209

Asia WGS AF: 0.135 AC: 470 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	-0.80
CADD	Benign	7.1
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2304188; hg19: chr19-40742105;