rs1063843

Variant names:

• chr12-121243884-T-C
• rs1063843
• ENST00000392473.2:c.*240A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 31 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=-0.92).
• 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 rank	MANE	Protein	UniProt
CAMKK2	NM_001270485.2	c.1596+689A>G		intron_variant	Intron 16 of 16	ENST00000404169.8	NP_001257414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMKK2	ENST00000404169.8	c.1596+689A>G		intron_variant	Intron 16 of 16	1	NM_001270485.2	ENSP00000384600.3

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

African (AFR) AF: 0.807 AC: 21503 AN: 26662

American (AMR) AF: 0.760 AC: 12519 AN: 16474

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 14192 AN: 16930

East Asian (EAS) AF: 0.686 AC: 20871 AN: 30408

South Asian (SAS) AF: 0.691 AC: 37887 AN: 54868

European-Finnish (FIN) AF: 0.848 AC: 22731 AN: 26810

Middle Eastern (MID) AF: 0.755 AC: 2502 AN: 3314

European-Non Finnish (NFE) AF: 0.802 AC: 795191 AN: 991834

Other (OTH) AF: 0.792 AC: 39376 AN: 49712

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

African (AFR) AF: 0.813 AC: 33748 AN: 41510

American (AMR) AF: 0.767 AC: 11725 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 2904 AN: 3472

East Asian (EAS) AF: 0.693 AC: 3586 AN: 5172

South Asian (SAS) AF: 0.686 AC: 3302 AN: 4812

European-Finnish (FIN) AF: 0.846 AC: 8967 AN: 10596

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.801 AC: 54450 AN: 67986

Other (OTH) AF: 0.780 AC: 1647 AN: 2112

Alfa AF: 0.795 Hom.: 202651

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
PhyloP100		-0.56
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: rs1063843; hg19: chr12-121681687;