chr12-121274173-G-A
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_001270485.2(CAMKK2):c.354C>T(p.Asn118=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,600,038 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0084 ( 19 hom., cov: 32)
Exomes 𝑓: 0.00095 ( 26 hom. )
Consequence
CAMKK2
NM_001270485.2 synonymous
NM_001270485.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.524
Genes affected
CAMKK2 (HGNC:1470): (calcium/calmodulin dependent protein kinase kinase 2) The product of this gene belongs to the Serine/Threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. The major isoform of this gene plays a role in the calcium/calmodulin-dependent (CaM) kinase cascade by phosphorylating the downstream kinases CaMK1 and CaMK4. Protein products of this gene also phosphorylate AMP-activated protein kinase (AMPK). This gene has its strongest expression in the brain and influences signalling cascades involved with learning and memory, neuronal differentiation and migration, neurite outgrowth, and synapse formation. Alternative splicing results in multiple transcript variants encoding distinct isoforms. The identified isoforms differ in their ability to undergo autophosphorylation and to phosphorylate downstream kinases. [provided by RefSeq, Jul 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
Variant 12-121274173-G-A is Benign according to our data. Variant chr12-121274173-G-A is described in ClinVar as [Benign]. Clinvar id is 709905.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.524 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00845 (1286/152194) while in subpopulation AFR AF= 0.0287 (1191/41522). AF 95% confidence interval is 0.0273. There are 19 homozygotes in gnomad4. There are 622 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1282 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAMKK2 | NM_001270485.2 | c.354C>T | p.Asn118= | synonymous_variant | 2/17 | ENST00000404169.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAMKK2 | ENST00000404169.8 | c.354C>T | p.Asn118= | synonymous_variant | 2/17 | 1 | NM_001270485.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00843 AC: 1282AN: 152078Hom.: 19 Cov.: 32
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GnomAD3 exomes AF: 0.00239 AC: 559AN: 233418Hom.: 8 AF XY: 0.00172 AC XY: 218AN XY: 127046
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GnomAD4 exome AF: 0.000954 AC: 1381AN: 1447844Hom.: 26 Cov.: 31 AF XY: 0.000830 AC XY: 596AN XY: 718228
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 20, 2018 | - - |
Computational scores
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Name
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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