rs41275750

Positions:

• chr19-40232188-C-G

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
AKT2	NM_001626.6	c.*1684G>C		3_prime_UTR_variant	14/14	ENST00000392038.7	NP_001617.1
AKT2	NM_001243027.3	c.*1684G>C		3_prime_UTR_variant	14/14		NP_001229956.1
AKT2	NM_001243028.3	c.*1684G>C		3_prime_UTR_variant	13/13		NP_001229957.1
AKT2	NM_001330511.1	c.*1684G>C		3_prime_UTR_variant	12/12		NP_001317440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKT2	ENST00000392038.7	c.*1684G>C		3_prime_UTR_variant	14/14	1	NM_001626.6	ENSP00000375892	P1
AKT2	ENST00000424901.5	c.*1684G>C		3_prime_UTR_variant	13/13	5		ENSP00000399532

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

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.0775

Gnomad4 ASJ exome AF: 0.0753

Gnomad4 EAS exome AF: 0.0588

Gnomad4 SAS exome AF: 0.0746

Gnomad4 FIN exome AF: 0.0489

Gnomad4 NFE exome AF: 0.0753

Gnomad4 OTH exome AF: 0.0923

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

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.0763

Gnomad4 ASJ AF: 0.0782

Gnomad4 EAS AF: 0.0529

Gnomad4 SAS AF: 0.0649

Gnomad4 FIN AF: 0.0539

Gnomad4 NFE AF: 0.0740

Gnomad4 OTH AF: 0.118

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

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: rs41275750; hg19: chr19-40738095;