Variant rs3817190 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMKK2	NM_001270485.2 linkuse as main transcript	c.253A>T	p.Thr85Ser	missense_variant	2/17	ENST00000404169.8	NP_001257414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMKK2	ENST00000404169.8 linkuse as main transcript	c.253A>T	p.Thr85Ser	missense_variant	2/17	1	NM_001270485.2	ENSP00000384600	P3	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

GnomAD3 exomes

AF:

0.377

AC:

91676

AN:

242952

Hom.:

18251

AF XY:

0.381

AC XY:

50441

AN XY:

132536

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 SAS exome

AF:

0.372

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

Gnomad4 AFR exome

AF:

0.581

Gnomad4 AMR exome

AF:

0.237

Gnomad4 ASJ exome

AF:

0.469

Gnomad4 EAS exome

AF:

0.336

Gnomad4 SAS exome

AF:

0.376

Gnomad4 FIN exome

AF:

0.354

Gnomad4 NFE exome

AF:

0.411

Gnomad4 OTH exome

AF:

0.409

GnomAD4 genome

AF:

0.442

AC:

67040

AN:

151740

Hom.:

15551

Cov.:

AF XY:

0.436

AC XY:

32344

AN XY:

74158

show subpopulations

Gnomad4 AFR

AF:

0.578

Gnomad4 AMR

AF:

0.362

Gnomad4 ASJ

AF:

0.481

Gnomad4 EAS

AF:

0.301

Gnomad4 SAS

AF:

0.342

Gnomad4 FIN

AF:

0.346

Gnomad4 NFE

AF:

0.407

Gnomad4 OTH

AF:

0.411

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.12

DANN

Benign

0.28

DEOGEN2

Benign

0.096

.;.;.;.;T;.;T;T;.;.;T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.30

T;T;T;.;.;T;.;T;T;T;T;T

MetaRNN

Benign

0.000013

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.34

N;N;N;N;N;N;N;N;N;N;.;.

MutationTaster

Benign

1.0

P;P;P;P;P;P;P;P;P

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.070

N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.45

T;T;T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.84

T;T;T;T;T;T;T;T;T;T;T;.

Polyphen

0.0

B;B;B;B;B;B;B;B;B;B;.;.

Vest4

0.053

MutPred

0.15

Gain of catalytic residue at L83 (P = 0.0259);Gain of catalytic residue at L83 (P = 0.0259);Gain of catalytic residue at L83 (P = 0.0259);Gain of catalytic residue at L83 (P = 0.0259);Gain of catalytic residue at L83 (P = 0.0259);Gain of catalytic residue at L83 (P = 0.0259);Gain of catalytic residue at L83 (P = 0.0259);Gain of catalytic residue at L83 (P = 0.0259);Gain of catalytic residue at L83 (P = 0.0259);Gain of catalytic residue at L83 (P = 0.0259);Gain of catalytic residue at L83 (P = 0.0259);Gain of catalytic residue at L83 (P = 0.0259);

MPC

0.33

ClinPred

0.0046

GERP RS

-0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.034

gMVP

0.17

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over