rs150000674
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2
The NM_001626.6(AKT2):c.945G>A(p.Glu315=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,613,974 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0017 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 3 hom. )
Consequence
AKT2
NM_001626.6 synonymous
NM_001626.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.498
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 19-40236272-C-T is Benign according to our data. Variant chr19-40236272-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 434116.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Likely_benign=1, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=0.498 with no splicing effect.
BS2
?
High AC in GnomAd4 at 260 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AKT2 | NM_001626.6 | c.945G>A | p.Glu315= | synonymous_variant | 10/14 | ENST00000392038.7 | |
AKT2 | NM_001243027.3 | c.759G>A | p.Glu253= | synonymous_variant | 10/14 | ||
AKT2 | NM_001243028.3 | c.759G>A | p.Glu253= | synonymous_variant | 9/13 | ||
AKT2 | NM_001330511.1 | c.832-168G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKT2 | ENST00000392038.7 | c.945G>A | p.Glu315= | synonymous_variant | 10/14 | 1 | NM_001626.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00171 AC: 260AN: 152204Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00185 AC: 465AN: 251380Hom.: 2 AF XY: 0.00180 AC XY: 244AN XY: 135900
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GnomAD4 exome AF: 0.00111 AC: 1629AN: 1461652Hom.: 3 Cov.: 36 AF XY: 0.00106 AC XY: 769AN XY: 727126
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GnomAD4 genome ? AF: 0.00171 AC: 260AN: 152322Hom.: 1 Cov.: 32 AF XY: 0.00248 AC XY: 185AN XY: 74500
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Type 2 diabetes mellitus Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | Potent mutationsin AKT2 gene are associated with familial partial lipodystrophy and in terms of metabolic abnormality, can present with insulin resistance, hyperglycemia and diabetes.However, more evidence is required to confer the association of this particular variant rs150000674 with Diabetes - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 22, 2016 | - - |
Type 2 diabetes mellitus;C3278384:Hypoinsulinemic hypoglycemia and body hemihypertrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2022 | AKT2: BS1, BS2 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at