chr19-40235130-T-A

Variant names:

• chr19-40235130-T-A
• NM_001626.6:c.1281A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001626.6(AKT2):​c.1281A>T​(p.Lys427Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: AKT2 NM_001626.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKT2	NM_001626.6	c.1281A>T	p.Lys427Asn	missense_variant	Exon 13 of 14	ENST00000392038.7	NP_001617.1
AKT2	NM_001330511.1	c.1152A>T	p.Lys384Asn	missense_variant	Exon 11 of 12		NP_001317440.1
AKT2	NM_001243027.3	c.1095A>T	p.Lys365Asn	missense_variant	Exon 13 of 14		NP_001229956.1
AKT2	NM_001243028.3	c.1095A>T	p.Lys365Asn	missense_variant	Exon 12 of 13		NP_001229957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKT2	ENST00000392038.7	c.1281A>T	p.Lys427Asn	missense_variant	Exon 13 of 14	1	NM_001626.6	ENSP00000375892.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Pathogenic	0.86	D;.;.;.;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.90	D;D;D;.;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.41	T;T;T;T;T;T
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.6	M;.;.;.;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-4.1	D;.;.;D;.;.
REVEL	Benign	0.24
Sift	Benign	0.090	T;.;.;T;.;.
Sift4G	Benign	0.22	T;T;D;T;T;.
Polyphen		0.62	P;.;.;.;.;.
Vest4		0.73
MutPred		0.42		Loss of methylation at K427 (P = 0.0024);.;.;.;.;.;
MVP		0.64
MPC		1.1
ClinPred		0.97	D
GERP RS		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.81
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: -7

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-40741037;