chr19-40233814-G-A

Variant names:

• chr19-40233814-G-A
• rs2304186
• ENST00000391844.8:n.*1118C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000391844.8(AKT2):​n.*1118C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000703 in 1,423,128 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: AKT2 ENST00000391844.8 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362
• Publications: 32 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKT2	NM_001626.6	c.*58C>T		3_prime_UTR_variant	Exon 14 of 14	ENST00000392038.7	NP_001617.1
AKT2	NM_001330511.1	c.*58C>T		3_prime_UTR_variant	Exon 12 of 12		NP_001317440.1
AKT2	NM_001243027.3	c.*58C>T		3_prime_UTR_variant	Exon 14 of 14		NP_001229956.1
AKT2	NM_001243028.3	c.*58C>T		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.*58C>T		3_prime_UTR_variant	Exon 14 of 14	1	NM_001626.6	ENSP00000375892.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000703 AC: 10 AN: 1423128 Hom.: 0 Cov.: 28 AF XY: 0.0000113 AC XY: 8 AN XY: 708088

African (AFR) AF: 0.00 AC: 0 AN: 32920

American (AMR) AF: 0.00 AC: 0 AN: 44284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25804

East Asian (EAS) AF: 0.00 AC: 0 AN: 39342

South Asian (SAS) AF: 0.000105 AC: 9 AN: 85508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 9.18e-7 AC: 1 AN: 1089030

Other (OTH) AF: 0.00 AC: 0 AN: 59234

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 18015

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.53
PhyloP100		-0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2304186; hg19: chr19-40739721;