rs3817190

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001270485.2(CAMKK2):c.253A>T(p.Thr85Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,611,448 control chromosomes in the GnomAD database, including 136,995 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.44 ( 15551 hom., cov: 32)

Exomes 𝑓: 0.40 ( 121444 hom. )

Consequence

CAMKK2
NM_001270485.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.550

Publications

40 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2945249E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

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.253A>T	p.Thr85Ser	missense	Exon 2 of 17	NP_001257414.1	Q96RR4-1
CAMKK2	NM_006549.4		c.253A>T	p.Thr85Ser	missense	Exon 2 of 17	NP_006540.3
CAMKK2	NM_001270486.1		c.253A>T	p.Thr85Ser	missense	Exon 1 of 16	NP_001257415.1	Q96RR4-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CAMKK2	ENST00000404169.8	TSL:1 MANE Select	c.253A>T	p.Thr85Ser	missense	Exon 2 of 17	ENSP00000384600.3	Q96RR4-1
CAMKK2	ENST00000324774.9	TSL:1	c.253A>T	p.Thr85Ser	missense	Exon 2 of 17	ENSP00000312741.5	Q96RR4-1
CAMKK2	ENST00000402834.8	TSL:1	c.253A>T	p.Thr85Ser	missense	Exon 2 of 17	ENSP00000384591.4	Q96RR4-1

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

66969

AN:

151624

Hom.:

15519

Cov.:

show subpopulations

Gnomad AFR

AF:

0.577

Gnomad AMI

AF:

0.587

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.481

Gnomad EAS

AF:

0.301

Gnomad SAS

AF:

0.342

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.395

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.416

GnomAD2 exomes

AF:

0.377

AC:

91676

AN:

242952

AF XY:

0.381

show subpopulations

Gnomad AFR exome

AF:

0.579

Gnomad AMR exome

AF:

0.225

Gnomad ASJ exome

AF:

0.470

Gnomad EAS exome

AF:

0.283

Gnomad FIN exome

AF:

0.352

Gnomad NFE exome

AF:

0.409

Gnomad OTH exome

AF:

0.396

GnomAD4 exome

AF:

0.404

AC:

589837

AN:

1459708

Hom.:

121444

Cov.:

AF XY:

0.403

AC XY:

292663

AN XY:

726112

show subpopulations

African (AFR)

AF:

0.581

AC:

19430

AN:

33466

American (AMR)

AF:

0.237

AC:

10567

AN:

44522

Ashkenazi Jewish (ASJ)

AF:

0.469

AC:

12237

AN:

26086

East Asian (EAS)

AF:

0.336

AC:

13330

AN:

39630

South Asian (SAS)

AF:

0.376

AC:

32365

AN:

86164

European-Finnish (FIN)

AF:

0.354

AC:

18594

AN:

52582

Middle Eastern (MID)

AF:

0.423

AC:

2437

AN:

5762

European-Non Finnish (NFE)

AF:

0.411

AC:

456250

AN:

1111244

Other (OTH)

AF:

0.409

AC:

24627

AN:

60252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

20178

40356

60534

80712

100890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14080

28160

42240

56320

70400

<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:

0.442

AC:

67040

AN:

151740

Hom.:

15551

Cov.:

AF XY:

0.436

AC XY:

32344

AN XY:

74158

show subpopulations

African (AFR)

AF:

0.578

AC:

23918

AN:

41412

American (AMR)

AF:

0.362

AC:

5528

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.481

AC:

1668

AN:

3468

East Asian (EAS)

AF:

0.301

AC:

1542

AN:

5126

South Asian (SAS)

AF:

0.342

AC:

1644

AN:

4804

European-Finnish (FIN)

AF:

0.346

AC:

3642

AN:

10518

Middle Eastern (MID)

AF:

0.401

AC:

117

AN:

292

European-Non Finnish (NFE)

AF:

0.407

AC:

27584

AN:

67840

Other (OTH)

AF:

0.411

AC:

864

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1902

3804

5706

7608

9510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

604

1208

1812

2416

3020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.415

Hom.:

4310

Bravo

AF:

0.447

TwinsUK

AF:

0.407

AC:

1510

ALSPAC

AF:

0.421

AC:

1622

ESP6500AA

AF:

0.561

AC:

2469

ESP6500EA

AF:

0.412

AC:

3539

ExAC

AF:

0.383

AC:

46265

Asia WGS

AF:

0.299

AC:

1040

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.12

(source)

DANN

Benign

0.28

DEOGEN2

Benign

0.096

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.30

MetaRNN

Benign

0.000013

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.34

PhyloP100

-0.55

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.070

REVEL

Benign

0.10

Sift

Benign

0.45

Sift4G

Benign

0.84

Polyphen

0.0

Vest4

0.053

MutPred

0.15

Gain of catalytic residue at L83 (P = 0.0259)

MPC

0.33

ClinPred

0.0046

GERP RS

-0.59

PromoterAI

-0.0058

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.034

gMVP

0.17

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over