12-121242657-G-C

Variant names:

• chr12-121242657-G-C
• rs11065504
• NM_001270485.2:c.1597-1788C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270485.2(CAMKK2):​c.1597-1788C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,162 control chromosomes in the GnomAD database, including 7,114 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 0.29 (7114 hom., cov: 32)
• Consequence: CAMKK2 NM_001270485.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.527
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.341 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMKK2	NM_001270485.2	MANE Select	c.1597-1788C>G		intron	N/A	NP_001257414.1	Q96RR4-1
	CAMKK2	NM_006549.4		c.1597-1788C>G		intron	N/A	NP_006540.3
	CAMKK2	NM_001270486.1		c.1596+1916C>G		intron	N/A	NP_001257415.1	Q96RR4-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMKK2	ENST00000404169.8	TSL:1 MANE Select	c.1597-1788C>G		intron	N/A	ENSP00000384600.3	Q96RR4-1
	CAMKK2	ENST00000324774.9	TSL:1	c.1597-1788C>G		intron	N/A	ENSP00000312741.5	Q96RR4-1
	CAMKK2	ENST00000402834.8	TSL:1	c.1597-1788C>G		intron	N/A	ENSP00000384591.4	Q96RR4-1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44639 AN: 152044 Hom.: 7115 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.293 AC: 44644 AN: 152162 Hom.: 7114 Cov.: 32 AF XY: 0.293 AC XY: 21776 AN XY: 74380

African (AFR) AF: 0.184 AC: 7634 AN: 41512

American (AMR) AF: 0.330 AC: 5050 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1499 AN: 3472

East Asian (EAS) AF: 0.348 AC: 1802 AN: 5182

South Asian (SAS) AF: 0.178 AC: 858 AN: 4826

European-Finnish (FIN) AF: 0.298 AC: 3147 AN: 10572

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23446 AN: 67986

Other (OTH) AF: 0.329 AC: 694 AN: 2112

Alfa AF: 0.302 Hom.: 917

Bravo AF: 0.298

Asia WGS AF: 0.229 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.73
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11065504; hg19: chr12-121680460;