rs9805130

Positions:

• chr12-121277592-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270485.2(CAMKK2):​c.-59-3007C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,118 control chromosomes in the GnomAD database, including 15,147 homozygotes. 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: 𝑓 0.44 (15147 hom., cov: 33)
• Consequence: CAMKK2 NM_001270485.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMKK2	NM_001270485.2	c.-59-3007C>T		intron_variant		ENST00000404169.8	NP_001257414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMKK2	ENST00000404169.8	c.-59-3007C>T		intron_variant		1	NM_001270485.2	ENSP00000384600	P3

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66219 AN: 152002 Hom.: 15115 Cov.: 33

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.408

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.436 AC: 66289 AN: 152118 Hom.: 15147 Cov.: 33 AF XY: 0.430 AC XY: 31969 AN XY: 74374

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.402

Alfa AF: 0.405 Hom.: 15776

Bravo AF: 0.441

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.51

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

Other links and lift over

dbSNP: rs9805130; hg19: chr12-121715395;