NM_001270485.2:c.1736T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001270485.2(CAMKK2):c.1736T>C(p.Leu579Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,608,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

CAMKK2
NM_001270485.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.671

Publications

0 publications found

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]

CAMKK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026919484).

BP6

Variant 12-121240730-A-G is Benign according to our data. Variant chr12-121240730-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3484493.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270485.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CAMKK2	NM_001270485.2	MANE Select	c.1736T>C	p.Leu579Pro	missense	Exon 17 of 17	NP_001257414.1	Q96RR4-1
CAMKK2	NM_006549.4		c.1736T>C	p.Leu579Pro	missense	Exon 17 of 17	NP_006540.3
CAMKK2	NM_172216.2		c.1607T>C	p.Leu536Pro	missense	Exon 16 of 16	NP_757365.1	Q96RR4-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CAMKK2	ENST00000404169.8	TSL:1 MANE Select	c.1736T>C	p.Leu579Pro	missense	Exon 17 of 17	ENSP00000384600.3	Q96RR4-1
CAMKK2	ENST00000324774.9	TSL:1	c.1736T>C	p.Leu579Pro	missense	Exon 17 of 17	ENSP00000312741.5	Q96RR4-1
CAMKK2	ENST00000402834.8	TSL:1	c.1736T>C	p.Leu579Pro	missense	Exon 17 of 17	ENSP00000384591.4	Q96RR4-1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000298

AC:

AN:

235160

AF XY:

0.0000385

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000152

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000943

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.00000824

AC:

AN:

1455826

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

724544

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33234

American (AMR)

AF:

0.000184

AC:

AN:

43562

Ashkenazi Jewish (ASJ)

AF:

0.0000385

AC:

AN:

25970

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.0000233

AC:

AN:

85858

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50716

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110956

Other (OTH)

AF:

0.00

AC:

AN:

60138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.000589

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000415

AC:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.0050

(source)

DANN

Benign

0.32

DEOGEN2

Benign

0.15

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.30

M_CAP

Benign

0.041

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

-0.67

PrimateAI

Benign

0.32

PROVEAN

Benign

0.020

REVEL

Benign

0.18

Sift

Benign

0.28

Sift4G

Benign

0.12

Polyphen

0.0

Vest4

0.041

MutPred

0.28

Gain of catalytic residue at P578 (P = 8e-04)

MVP

0.63

MPC

0.59

ClinPred

0.038

GERP RS

-11

Varity_R

0.032

gMVP

0.28

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over