chr19-40254165-C-T

Variant names:

• chr19-40254165-C-T
• rs892119
• NM_001626.6:c.287+993G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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]

AKT2 Gene-Disease associations (from GenCC):

• hypoinsulinemic hypoglycemia and body hemihypertrophy

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• diabetes mellitus, noninsulin-dependent

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• AKT2-related familial partial lipodystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• type 2 diabetes mellitus

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

LOC107985289 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AKT2	NM_001626.6	c.287+993G>A		intron_variant	Intron 4 of 13	ENST00000392038.7	NP_001617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKT2	ENST00000392038.7	c.287+993G>A		intron_variant	Intron 4 of 13	1	NM_001626.6	ENSP00000375892.2

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

African (AFR) AF: 0.206 AC: 8452 AN: 40940

American (AMR) AF: 0.179 AC: 2157 AN: 12040

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 507 AN: 3120

East Asian (EAS) AF: 0.164 AC: 701 AN: 4266

South Asian (SAS) AF: 0.153 AC: 502 AN: 3284

European-Finnish (FIN) AF: 0.228 AC: 2055 AN: 9000

Middle Eastern (MID) AF: 0.171 AC: 43 AN: 252

European-Non Finnish (NFE) AF: 0.181 AC: 10324 AN: 57092

Other (OTH) AF: 0.185 AC: 338 AN: 1824

Alfa AF: 0.156 Hom.: 1057

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
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs892119; hg19: chr19-40760072;