chr19-40282734-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.892 AC: 2983 AN: 3344

American (AMR) AF: 0.756 AC: 5666 AN: 7496

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2357 AN: 3664

East Asian (EAS) AF: 0.656 AC: 2982 AN: 4544

South Asian (SAS) AF: 0.763 AC: 30367 AN: 39784

European-Finnish (FIN) AF: 0.673 AC: 11000 AN: 16348

Middle Eastern (MID) AF: 0.720 AC: 724 AN: 1006

European-Non Finnish (NFE) AF: 0.703 AC: 67770 AN: 96434

Other (OTH) AF: 0.716 AC: 5962 AN: 8332

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

African (AFR) AF: 0.906 AC: 37617 AN: 41498

American (AMR) AF: 0.758 AC: 11583 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2232 AN: 3472

East Asian (EAS) AF: 0.670 AC: 3457 AN: 5158

South Asian (SAS) AF: 0.769 AC: 3709 AN: 4826

European-Finnish (FIN) AF: 0.655 AC: 6928 AN: 10578

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47649 AN: 67982

Other (OTH) AF: 0.739 AC: 1557 AN: 2108

Alfa AF: 0.731 Hom.: 16561

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
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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