rs56131600

Variant names:

• chr12-121253327-G-A
• rs56131600
• NM_001270485.2:c.1053C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001270485.2(CAMKK2):​c.1053C>T​(p.Pro351Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00539 in 1,614,162 control chromosomes in the GnomAD database, including 368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (200 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (168 hom.)
• Consequence: CAMKK2 NM_001270485.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.52
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 12-121253327-G-A is Benign according to our data. Variant chr12-121253327-G-A is described in ClinVar as Benign. ClinVar VariationId is 781092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.52 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0917 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.1053C>T	p.Pro351Pro	synonymous	Exon 10 of 17	NP_001257414.1	Q96RR4-1
	CAMKK2	NM_006549.4		c.1053C>T	p.Pro351Pro	synonymous	Exon 10 of 17	NP_006540.3
	CAMKK2	NM_001270486.1		c.1053C>T	p.Pro351Pro	synonymous	Exon 9 of 16	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.1053C>T	p.Pro351Pro	synonymous	Exon 10 of 17	ENSP00000384600.3	Q96RR4-1
	CAMKK2	ENST00000324774.9	TSL:1	c.1053C>T	p.Pro351Pro	synonymous	Exon 10 of 17	ENSP00000312741.5	Q96RR4-1
	CAMKK2	ENST00000402834.8	TSL:1	c.1053C>T	p.Pro351Pro	synonymous	Exon 10 of 17	ENSP00000384591.4	Q96RR4-1

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4147 AN: 152168 Hom.: 199 Cov.: 32

Gnomad AFR AF: 0.0941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00890

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.0186

GnomAD2 exomes AF: 0.00790 AC: 1987 AN: 251464 AF XY: 0.00592

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.00538

Gnomad ASJ exome AF: 0.000992

Gnomad EAS exome AF: 0.00256

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000563

Gnomad OTH exome AF: 0.00407

GnomAD4 exome AF: 0.00310 AC: 4539 AN: 1461876 Hom.: 168 Cov.: 33 AF XY: 0.00272 AC XY: 1975 AN XY: 727240

African (AFR) AF: 0.0946 AC: 3166 AN: 33476

American (AMR) AF: 0.00617 AC: 276 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000804 AC: 21 AN: 26134

East Asian (EAS) AF: 0.00146 AC: 58 AN: 39700

South Asian (SAS) AF: 0.000522 AC: 45 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00676 AC: 39 AN: 5768

European-Non Finnish (NFE) AF: 0.000478 AC: 531 AN: 1112004

Other (OTH) AF: 0.00666 AC: 402 AN: 60394

GnomAD4 genome AF: 0.0273 AC: 4161 AN: 152286 Hom.: 200 Cov.: 32 AF XY: 0.0258 AC XY: 1918 AN XY: 74472

African (AFR) AF: 0.0942 AC: 3914 AN: 41554

American (AMR) AF: 0.00889 AC: 136 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5186

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000676 AC: 46 AN: 68016

Other (OTH) AF: 0.0184 AC: 39 AN: 2114

Alfa AF: 0.0123 Hom.: 64

Bravo AF: 0.0315

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.00113

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.1
DANN	Benign	0.75
PhyloP100		-3.5
Mutation Taster		=98/2	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: rs56131600; hg19: chr12-121691130;