rs11880261

Variant names:

• chr19-40282734-T-C
• rs11880261
• NM_001626.6:c.-85+2447A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001626.6(AKT2):​c.-85+2447A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 333,054 control chromosomes in the GnomAD database, including 91,528 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 0.76 (44631 hom., cov: 32)
  • Exomes 𝑓: 0.72 (46897 hom.)
• Consequence: AKT2 NM_001626.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495

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]

MIR641 (HGNC:32897): (microRNA 641) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKT2	NM_001626.6	c.-85+2447A>G		intron_variant	Intron 1 of 13	ENST00000392038.7	NP_001617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKT2	ENST00000392038.7	c.-85+2447A>G		intron_variant	Intron 1 of 13	1	NM_001626.6	ENSP00000375892.2

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115502 AN: 151982 Hom.: 44592 Cov.: 32

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.740

GnomAD4 exome AF: 0.717 AC: 129811 AN: 180952 Hom.: 46897 Cov.: 0 AF XY: 0.724 AC XY: 72238 AN XY: 99836

Gnomad4 AFR exome AF: 0.892

Gnomad4 AMR exome AF: 0.756

Gnomad4 ASJ exome AF: 0.643

Gnomad4 EAS exome AF: 0.656

Gnomad4 SAS exome AF: 0.763

Gnomad4 FIN exome AF: 0.673

Gnomad4 NFE exome AF: 0.703

Gnomad4 OTH exome AF: 0.716

GnomAD4 genome AF: 0.760 AC: 115603 AN: 152102 Hom.: 44631 Cov.: 32 AF XY: 0.757 AC XY: 56254 AN XY: 74340

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.739

Alfa AF: 0.734 Hom.: 10755

Bravo AF: 0.772

Asia WGS AF: 0.743 AC: 2584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.1
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs11880261; hg19: chr19-40788641; COSMIC: COSV64225022; COSMIC: COSV64225022;