dbSNP rs7254617: AKT2:n.-555C>T (chr19-40285605-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000391844.8(AKT2):n.-555C>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
ENST00000391844.8 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.944

Publications

14 publications found

Variant links:

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)

AKT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	TSL	Protein
AKT2	ENST00000391844.8 link	n.-555C>T	upstream_gene_variant	1	ENSP00000375719.4
AKT2	ENST00000424901.5 link	c.-509C>T	upstream_gene_variant	5	ENSP00000399532.2
AKT2	ENST00000578123.5 link	c.-242C>T	upstream_gene_variant	4	ENSP00000462022.1

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32900

AN:

151924

Hom.:

4338

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.366

AC:

2175

AN:

5936

American (AMR)

AF:

0.127

AC:

763

AN:

6008

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

1295

AN:

7614

East Asian (EAS)

AF:

0.153

AC:

2943

AN:

19232

South Asian (SAS)

AF:

0.109

AC:

203

AN:

1862

European-Finnish (FIN)

AF:

0.202

AC:

3686

AN:

18272

Middle Eastern (MID)

AF:

0.147

AC:

158

AN:

1072

European-Non Finnish (NFE)

AF:

0.156

AC:

20635

AN:

132314

Other (OTH)

AF:

0.180

AC:

2431

AN:

13490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1287

2574

3860

5147

6434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.217

AC:

32957

AN:

152042

Hom.:

4355

Cov.:

AF XY:

0.214

AC XY:

15936

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.367

AC:

15219

AN:

41460

American (AMR)

AF:

0.161

AC:

2455

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

587

AN:

3470

East Asian (EAS)

AF:

0.137

AC:

709

AN:

5162

South Asian (SAS)

AF:

0.105

AC:

506

AN:

4818

European-Finnish (FIN)

AF:

0.195

AC:

2064

AN:

10572

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.158

AC:

10711

AN:

67950

Other (OTH)

AF:

0.199

AC:

420

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1244

2488

3731

4975

6219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.80

PhyloP100

-0.94

PromoterAI

0.037

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over