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12-121255566-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001270485.2(CAMKK2):c.891C>T(p.Ile297=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,611,374 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 Benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 29)
Exomes 𝑓: 0.0013 ( 4 hom. )

Consequence

CAMKK2
NM_001270485.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.66
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 -9 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=-0.37).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-121255566-G-A is Benign according to our data. Variant chr12-121255566-G-A is described in ClinVar as [Benign]. Clinvar id is 771186.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=1.66 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 159 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CAMKK2NM_001270485.2 linkuse as main transcriptc.891C>T p.Ile297= synonymous_variant 9/17 ENST00000404169.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CAMKK2ENST00000404169.8 linkuse as main transcriptc.891C>T p.Ile297= synonymous_variant 9/171 NM_001270485.2 P3Q96RR4-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00105
AC:
159
AN:
150966
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.000244
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00174
Gnomad ASJ
AF:
0.00317
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0222
Gnomad NFE
AF:
0.00146
Gnomad OTH
AF:
0.00241
GnomAD3 exomes
AF:
0.00145
AC:
360
AN:
248752
Hom.:
0
AF XY:
0.00152
AC XY:
204
AN XY:
134414
show subpopulations
Gnomad AFR exome
AF:
0.000251
Gnomad AMR exome
AF:
0.00204
Gnomad ASJ exome
AF:
0.00121
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000665
Gnomad FIN exome
AF:
0.000327
Gnomad NFE exome
AF:
0.00191
Gnomad OTH exome
AF:
0.00527
GnomAD4 exome
AF:
0.00135
AC:
1971
AN:
1460290
Hom.:
4
Cov.:
30
AF XY:
0.00140
AC XY:
1015
AN XY:
726236
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.00173
Gnomad4 ASJ exome
AF:
0.00165
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000735
Gnomad4 FIN exome
AF:
0.000244
Gnomad4 NFE exome
AF:
0.00141
Gnomad4 OTH exome
AF:
0.00224
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00105
AC:
158
AN:
151084
Hom.:
0
Cov.:
29
AF XY:
0.000868
AC XY:
64
AN XY:
73742
show subpopulations
Gnomad4 AFR
AF:
0.000243
Gnomad4 AMR
AF:
0.00174
Gnomad4 ASJ
AF:
0.00317
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00146
Gnomad4 OTH
AF:
0.00239
Alfa
AF:
0.00131
Hom.:
0
Bravo
AF:
0.00134

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 testingInvitaeJun 06, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
Cadd
Benign
12
Dann
Benign
0.82

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: rs139606987; hg19: chr12-121693369; COSMIC: COSV61212616; API