ENST00000579047.5:c.1286A>C

Variant names:

• chr19-40234939-T-G
• ENST00000579047.5:c.1286A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000579047.5(AKT2):​c.1286A>C​(p.His429Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000227 in 882,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/11 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H429R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: AKT2 ENST00000579047.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13370982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKT2	NM_001626.6	c.1366+106A>C		intron_variant	Intron 13 of 13	ENST00000392038.7	NP_001617.1
AKT2	NM_001330511.1	c.1237+106A>C		intron_variant	Intron 11 of 11		NP_001317440.1
AKT2	NM_001243027.3	c.1180+106A>C		intron_variant	Intron 13 of 13		NP_001229956.1
AKT2	NM_001243028.3	c.1180+106A>C		intron_variant	Intron 12 of 12		NP_001229957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKT2	ENST00000392038.7	c.1366+106A>C		intron_variant	Intron 13 of 13	1	NM_001626.6	ENSP00000375892.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000227 AC: 2 AN: 882674 Hom.: 0 Cov.: 12 AF XY: 0.00000219 AC XY: 1 AN XY: 456782

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: 0.00000331

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	0.046
DANN	Benign	0.57
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.13	T
Sift4G	Pathogenic	0.0	D
Vest4		0.13
MVP		0.78
GERP RS		-5.1

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-40740846;