rs41275750

Variant names:

• chr19-40232188-C-G
• rs41275750
• NM_001626.6:c.*1684G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001626.6(AKT2):​c.*1684G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 233,642 control chromosomes in the GnomAD database, including 2,315 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 0.13 (1896 hom., cov: 32)
  • Exomes 𝑓: 0.085 (419 hom.)
• Consequence: AKT2 NM_001626.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 10 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKT2	NM_001626.6	c.*1684G>C		3_prime_UTR_variant	Exon 14 of 14	ENST00000392038.7	NP_001617.1
AKT2	NM_001330511.1	c.*1684G>C		3_prime_UTR_variant	Exon 12 of 12		NP_001317440.1
AKT2	NM_001243027.3	c.*1684G>C		3_prime_UTR_variant	Exon 14 of 14		NP_001229956.1
AKT2	NM_001243028.3	c.*1684G>C		3_prime_UTR_variant	Exon 13 of 13		NP_001229957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKT2	ENST00000392038.7	c.*1684G>C		3_prime_UTR_variant	Exon 14 of 14	1	NM_001626.6	ENSP00000375892.2
AKT2	ENST00000424901.5	c.*1684G>C		3_prime_UTR_variant	Exon 13 of 13	5		ENSP00000399532.2
AKT2	ENST00000476266.5	n.*149G>C		downstream_gene_variant		5
AKT2	ENST00000483166.5	n.*147G>C		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19270 AN: 151898 Hom.: 1892 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.0764

Gnomad ASJ AF: 0.0782

Gnomad EAS AF: 0.0536

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0740

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.0850 AC: 6939 AN: 81628 Hom.: 419 Cov.: 0 AF XY: 0.0840 AC XY: 3164 AN XY: 37650

African (AFR) AF: 0.291 AC: 1135 AN: 3904

American (AMR) AF: 0.0775 AC: 194 AN: 2502

Ashkenazi Jewish (ASJ) AF: 0.0753 AC: 386 AN: 5124

East Asian (EAS) AF: 0.0588 AC: 671 AN: 11410

South Asian (SAS) AF: 0.0746 AC: 53 AN: 710

European-Finnish (FIN) AF: 0.0489 AC: 23 AN: 470

Middle Eastern (MID) AF: 0.137 AC: 68 AN: 498

European-Non Finnish (NFE) AF: 0.0753 AC: 3783 AN: 50228

Other (OTH) AF: 0.0923 AC: 626 AN: 6782

GnomAD4 genome AF: 0.127 AC: 19286 AN: 152014 Hom.: 1896 Cov.: 32 AF XY: 0.125 AC XY: 9253 AN XY: 74300

African (AFR) AF: 0.273 AC: 11294 AN: 41414

American (AMR) AF: 0.0763 AC: 1166 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0782 AC: 271 AN: 3464

East Asian (EAS) AF: 0.0529 AC: 272 AN: 5138

South Asian (SAS) AF: 0.0649 AC: 312 AN: 4806

European-Finnish (FIN) AF: 0.0539 AC: 572 AN: 10612

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0740 AC: 5028 AN: 67990

Other (OTH) AF: 0.118 AC: 248 AN: 2110

Alfa AF: 0.105 Hom.: 170

Bravo AF: 0.135

Asia WGS AF: 0.0770 AC: 266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.4
DANN	Benign	0.79
PhyloP100		-0.057
Mutation Taster		=97/3	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: rs41275750; hg19: chr19-40738095;