rs2254266

Variant names:

• chr10-73841930-T-C
• rs2254266
• NM_001367534.1:c.946+239A>G

Variant summary

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

The NM_001367534.1(CAMK2G):​c.946+239A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 546,872 control chromosomes in the GnomAD database, including 10,906 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 0.18 (2615 hom., cov: 32)
  • Exomes 𝑓: 0.20 (8291 hom.)
• Consequence: CAMK2G NM_001367534.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443
• Publications: 11 publications found

Genes affected

CAMK2G (HGNC:1463): (calcium/calmodulin dependent protein kinase II gamma) The product of this gene is one of the four subunits of an enzyme which belongs to the serine/threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. In mammalian cells the enzyme is composed of four different chains: alpha, beta, gamma, and delta. The product of this gene is a gamma chain. Many alternatively spliced transcripts encoding different isoforms have been described but the full-length nature of all the variants has not been determined.[provided by RefSeq, Mar 2011]

CAMK2G Gene-Disease associations (from GenCC):

• intellectual developmental disorder 59

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000229990 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367534.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2G	NM_001367534.1	MANE Select	c.946+239A>G		intron	N/A	NP_001354463.1
	CAMK2G	NM_001320898.2		c.946+239A>G		intron	N/A	NP_001307827.1
	CAMK2G	NM_001367544.1		c.946+239A>G		intron	N/A	NP_001354473.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2G	ENST00000423381.6	TSL:5 MANE Select	c.946+239A>G		intron	N/A	ENSP00000410298.3
	CAMK2G	ENST00000322635.7	TSL:1	c.946+239A>G		intron	N/A	ENSP00000315599.3
	CAMK2G	ENST00000433289.5	TSL:1	c.751+239A>G		intron	N/A	ENSP00000393784.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27613 AN: 152074 Hom.: 2603 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.198 AC: 78186 AN: 394680 Hom.: 8291 Cov.: 0 AF XY: 0.203 AC XY: 42376 AN XY: 208378

African (AFR) AF: 0.172 AC: 1926 AN: 11184

American (AMR) AF: 0.114 AC: 1735 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 3606 AN: 12034

East Asian (EAS) AF: 0.214 AC: 5783 AN: 26990

South Asian (SAS) AF: 0.259 AC: 10770 AN: 41546

European-Finnish (FIN) AF: 0.179 AC: 4481 AN: 25022

Middle Eastern (MID) AF: 0.242 AC: 424 AN: 1754

European-Non Finnish (NFE) AF: 0.189 AC: 44991 AN: 238124

Other (OTH) AF: 0.196 AC: 4470 AN: 22838

GnomAD4 genome AF: 0.182 AC: 27657 AN: 152192 Hom.: 2615 Cov.: 32 AF XY: 0.179 AC XY: 13328 AN XY: 74408

African (AFR) AF: 0.172 AC: 7135 AN: 41510

American (AMR) AF: 0.131 AC: 2005 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1053 AN: 3470

East Asian (EAS) AF: 0.204 AC: 1059 AN: 5180

South Asian (SAS) AF: 0.244 AC: 1177 AN: 4828

European-Finnish (FIN) AF: 0.158 AC: 1678 AN: 10594

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12964 AN: 68004

Other (OTH) AF: 0.168 AC: 353 AN: 2104

Alfa AF: 0.193 Hom.: 11832

Bravo AF: 0.182

Asia WGS AF: 0.198 AC: 691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.8
DANN	Benign	0.62
PhyloP100		0.44
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: rs2254266; hg19: chr10-75601688;