rs35588791
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001626.6(AKT2):c.93C>T(p.Ser31=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,614,128 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0029 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0044 ( 37 hom. )
Consequence
AKT2
NM_001626.6 synonymous
NM_001626.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.00500
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 19-40257008-G-A is Benign according to our data. Variant chr19-40257008-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 434118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40257008-G-A is described in Lovd as [Likely_benign]. Variant chr19-40257008-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.005 with no splicing effect.
BS2
?
High AC in GnomAd4 at 446 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AKT2 | NM_001626.6 | c.93C>T | p.Ser31= | synonymous_variant | 3/14 | ENST00000392038.7 | |
AKT2 | NM_001330511.1 | c.93C>T | p.Ser31= | synonymous_variant | 2/12 | ||
AKT2 | NM_001243027.3 | c.-94C>T | 5_prime_UTR_variant | 3/14 | |||
AKT2 | NM_001243028.3 | c.-94C>T | 5_prime_UTR_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKT2 | ENST00000392038.7 | c.93C>T | p.Ser31= | synonymous_variant | 3/14 | 1 | NM_001626.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00294 AC: 447AN: 152202Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00357 AC: 898AN: 251480Hom.: 3 AF XY: 0.00413 AC XY: 562AN XY: 135914
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GnomAD4 exome AF: 0.00439 AC: 6413AN: 1461808Hom.: 37 Cov.: 32 AF XY: 0.00457 AC XY: 3324AN XY: 727212
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GnomAD4 genome ? AF: 0.00293 AC: 446AN: 152320Hom.: 1 Cov.: 32 AF XY: 0.00305 AC XY: 227AN XY: 74478
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 25, 2019 | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | AKT2: BP4, BP7, BS1, BS2 - |
Type 2 diabetes mellitus Benign:1
Likely benign, 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. In, silico analysis revealed that this particular rs35588791 is prevalent with Type 2 Diabetes - |
Type 2 diabetes mellitus;C3278384:Hypoinsulinemic hypoglycemia and body hemihypertrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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