chr19-40277925-T-G

Position:

• chr19-40277925-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001626.6(AKT2):​c.-85+7256A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0249 in 152,336 control chromosomes in the GnomAD database, including 85 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 0.025 (85 hom., cov: 32)
• Consequence: AKT2 NM_001626.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.624

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=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0249 (3797/152336) while in subpopulation NFE AF= 0.0407 (2766/68016). AF 95% confidence interval is 0.0394. There are 85 homozygotes in gnomad4. There are 1784 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3797 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKT2	NM_001626.6	c.-85+7256A>C		intron_variant		ENST00000392038.7
AKT2	NM_001243027.3	c.-234+7256A>C		intron_variant
AKT2	NM_001243028.3	c.-141+7256A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKT2	ENST00000392038.7	c.-85+7256A>C		intron_variant		1	NM_001626.6	P1

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3798 AN: 152218 Hom.: 85 Cov.: 32

Gnomad AFR AF: 0.00564

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.0358

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00372

Gnomad FIN AF: 0.0315

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0407

Gnomad OTH AF: 0.0263

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0249 AC: 3797 AN: 152336 Hom.: 85 Cov.: 32 AF XY: 0.0239 AC XY: 1784 AN XY: 74498

Gnomad4 AFR AF: 0.00563

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.0358

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.0315

Gnomad4 NFE AF: 0.0407

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0299 Hom.: 13

Bravo AF: 0.0238

Asia WGS AF: 0.00318 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.70

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: rs76137255; hg19: chr19-40783832;