chr19-40233960-G-A
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001626.6(AKT2):c.1367-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,609,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
AKT2
NM_001626.6 splice_polypyrimidine_tract, intron
NM_001626.6 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00002323
2
Clinical Significance
Conservation
PhyloP100: 0.668
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 -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 19-40233960-G-A is Benign according to our data. Variant chr19-40233960-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3038462.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AKT2 | NM_001626.6 | c.1367-9C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000392038.7 | |||
AKT2 | NM_001243027.3 | c.1181-9C>T | splice_polypyrimidine_tract_variant, intron_variant | ||||
AKT2 | NM_001243028.3 | c.1181-9C>T | splice_polypyrimidine_tract_variant, intron_variant | ||||
AKT2 | NM_001330511.1 | c.1238-9C>T | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKT2 | ENST00000392038.7 | c.1367-9C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001626.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152180Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000206 AC: 5AN: 242968Hom.: 0 AF XY: 0.0000151 AC XY: 2AN XY: 132104
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GnomAD4 exome AF: 0.00000824 AC: 12AN: 1457192Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 724996
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74338
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
AKT2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 28, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at