rs2686342

chr12-121247385-T-Achr12-121247385-T-C

Variant summary

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

The NM_001270485.2(CAMKK2):c.1452+1221A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,066 control chromosomes in the GnomAD database, including 43,909 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 0.76 (43909 hom., cov: 31)
• Consequence: CAMKK2 NM_001270485.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMKK2	NM_001270485.2	c.1452+1221A>T		intron_variant		ENST00000404169.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMKK2	ENST00000404169.8	c.1452+1221A>T		intron_variant		1	NM_001270485.2	P3

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115213 AN: 151946 Hom.: 43882 Cov.: 31

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.758 AC: 115283 AN: 152066 Hom.: 43909 Cov.: 31 AF XY: 0.759 AC XY: 56407 AN XY: 74346

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.751

Gnomad4 ASJ AF: 0.834

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.848

Gnomad4 NFE AF: 0.800

Gnomad4 OTH AF: 0.752

Alfa AF: 0.778 Hom.: 5425

Bravo AF: 0.751

Asia WGS AF: 0.659 AC: 2292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	3.7
Dann	Benign	0.75

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: rs2686342; hg19: chr12-121685188;