rs1063843

Positions:

• chr12-121243884-T-C

Variant summary

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

The ENST00000392473.2(CAMKK2):​c.*240A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 1,369,156 control chromosomes in the GnomAD database, including 433,287 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 0.80 (48382 hom., cov: 31)
  • Exomes 𝑓: 0.79 (384905 hom.)
• Consequence: CAMKK2 ENST00000392473.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMKK2	NM_001270485.2	c.1596+689A>G		intron_variant		ENST00000404169.8	NP_001257414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMKK2	ENST00000404169.8	c.1596+689A>G		intron_variant		1	NM_001270485.2	ENSP00000384600	P3

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121183 AN: 152026 Hom.: 48342 Cov.: 31

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.784

GnomAD4 exome AF: 0.794 AC: 966772 AN: 1217012 Hom.: 384905 Cov.: 33 AF XY: 0.791 AC XY: 464357 AN XY: 586882

Gnomad4 AFR exome AF: 0.807

Gnomad4 AMR exome AF: 0.760

Gnomad4 ASJ exome AF: 0.838

Gnomad4 EAS exome AF: 0.686

Gnomad4 SAS exome AF: 0.691

Gnomad4 FIN exome AF: 0.848

Gnomad4 NFE exome AF: 0.802

Gnomad4 OTH exome AF: 0.792

GnomAD4 genome AF: 0.797 AC: 121272 AN: 152144 Hom.: 48382 Cov.: 31 AF XY: 0.796 AC XY: 59232 AN XY: 74378

Gnomad4 AFR AF: 0.813

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.836

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.846

Gnomad4 NFE AF: 0.801

Gnomad4 OTH AF: 0.780

Alfa AF: 0.795 Hom.: 97998

Bravo AF: 0.796

Asia WGS AF: 0.666 AC: 2317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.49
DANN	Benign	0.46

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: rs1063843; hg19: chr12-121681687;