rs1057519754

Variant names:

• chr19-40236313-T-C
• rs1057519754
• NM_001626.6:c.904A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001626.6(AKT2):​c.904A>G​(p.Ser302Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,850 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AKT2 NM_001626.6 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.25

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31636354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKT2	NM_001626.6	c.904A>G	p.Ser302Gly	missense_variant	Exon 10 of 14	ENST00000392038.7	NP_001617.1
AKT2	NM_001243027.3	c.718A>G	p.Ser240Gly	missense_variant	Exon 10 of 14		NP_001229956.1
AKT2	NM_001243028.3	c.718A>G	p.Ser240Gly	missense_variant	Exon 9 of 13		NP_001229957.1
AKT2	NM_001330511.1	c.832-209A>G		intron_variant	Intron 8 of 11		NP_001317440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKT2	ENST00000392038.7	c.904A>G	p.Ser302Gly	missense_variant	Exon 10 of 14	1	NM_001626.6	ENSP00000375892.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461850 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Neoplasm of the large intestine Pathogenic:1

Jul 14, 2015

Database of Curated Mutations (DoCM)

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T;.;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.0014
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	T;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.1	L;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.0	D;.;.
REVEL	Benign	0.11
Sift	Benign	0.094	T;.;.
Sift4G	Benign	0.25	T;T;.
Polyphen		0.0	B;.;.
Vest4		0.19
MutPred		0.27		Gain of ubiquitination at K298 (P = 0.102);.;.;
MVP		0.64
MPC		0.82
ClinPred		0.85	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.64
gMVP		0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs1057519754; hg19: chr19-40742220;