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12-121274077-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001270485.2(CAMKK2):c.450C>T(p.His150=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000879 in 1,515,082 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00068 ( 7 hom. )

Consequence

CAMKK2
NM_001270485.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.79
Variant links:
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 -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-121274077-G-A is Benign according to our data. Variant chr12-121274077-G-A is described in ClinVar as [Benign]. Clinvar id is 773688.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.79 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 404 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CAMKK2NM_001270485.2 linkuse as main transcriptc.450C>T p.His150= synonymous_variant 2/17 ENST00000404169.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CAMKK2ENST00000404169.8 linkuse as main transcriptc.450C>T p.His150= synonymous_variant 2/171 NM_001270485.2 P3Q96RR4-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00265
AC:
404
AN:
152166
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00794
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000721
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00120
AC:
185
AN:
154226
Hom.:
3
AF XY:
0.000989
AC XY:
81
AN XY:
81868
show subpopulations
Gnomad AFR exome
AF:
0.00856
Gnomad AMR exome
AF:
0.000509
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000209
Gnomad SAS exome
AF:
0.000637
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000766
Gnomad OTH exome
AF:
0.000555
GnomAD4 exome
AF:
0.000677
AC:
923
AN:
1362798
Hom.:
7
Cov.:
31
AF XY:
0.000714
AC XY:
476
AN XY:
666676
show subpopulations
Gnomad4 AFR exome
AF:
0.00827
Gnomad4 AMR exome
AF:
0.000655
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000784
Gnomad4 SAS exome
AF:
0.000431
Gnomad4 FIN exome
AF:
0.0000208
Gnomad4 NFE exome
AF:
0.000482
Gnomad4 OTH exome
AF:
0.00159
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00268
AC:
408
AN:
152284
Hom.:
1
Cov.:
32
AF XY:
0.00271
AC XY:
202
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.00801
Gnomad4 AMR
AF:
0.00131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000721
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00228
Hom.:
0
Bravo
AF:
0.00295
Asia WGS
AF:
0.00318
AC:
11
AN:
3478

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 submitterclinical testingInvitaeJul 10, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
Cadd
Benign
7.5
Dann
Benign
0.72
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35407516; hg19: chr12-121711880; API