chr12-121250025-T-C

Variant names:

• chr12-121250025-T-C
• NM_001270485.2:c.1171A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001270485.2(CAMKK2):​c.1171A>G​(p.Met391Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAMKK2 NM_001270485.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.93

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21765381).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMKK2	NM_001270485.2	c.1171A>G	p.Met391Val	missense_variant	Exon 12 of 17	ENST00000404169.8	NP_001257414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMKK2	ENST00000404169.8	c.1171A>G	p.Met391Val	missense_variant	Exon 12 of 17	1	NM_001270485.2	ENSP00000384600.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	23
DANN	Benign	0.79
DEOGEN2	Benign	0.077	.;.;.;.;T;T;.;T;T;.;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.038
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	D;D;D;.;.;D;D;.;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.22	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.57	N;N;N;N;N;.;N;N;N;N;N
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.51	N;N;N;N;N;N;N;N;.;N;N
REVEL	Benign	0.17
Sift	Benign	0.65	T;T;T;T;T;T;T;T;.;T;T
Sift4G	Benign	0.54	T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.056	B;B;B;B;B;B;B;B;B;B;B
Vest4		0.41
MutPred		0.50		Gain of catalytic residue at Q387 (P = 0);Gain of catalytic residue at Q387 (P = 0);Gain of catalytic residue at Q387 (P = 0);Gain of catalytic residue at Q387 (P = 0);Gain of catalytic residue at Q387 (P = 0);.;Gain of catalytic residue at Q387 (P = 0);Gain of catalytic residue at Q387 (P = 0);Gain of catalytic residue at Q387 (P = 0);Gain of catalytic residue at Q387 (P = 0);Gain of catalytic residue at Q387 (P = 0);
MVP		0.82
MPC		0.42
ClinPred		0.40	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-121687828;