rs2242255

Variant names:

• chr10-73837531-T-A
• rs2242255
• NM_001367534.1:c.1010-20A>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001367534.1(CAMK2G):​c.1010-20A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,603,904 control chromosomes in the GnomAD database, including 29,082 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 (2485 hom., cov: 32)
  • Exomes 𝑓: 0.19 (26597 hom.)
• Consequence: CAMK2G NM_001367534.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 13 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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2G	NM_001367534.1	c.1010-20A>T		intron_variant	Intron 13 of 22	ENST00000423381.6	NP_001354463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK2G	ENST00000423381.6	c.1010-20A>T		intron_variant	Intron 13 of 22	5	NM_001367534.1	ENSP00000410298.3

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26868 AN: 151940 Hom.: 2473 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.164

GnomAD2 exomes AF: 0.189 AC: 47533 AN: 251492 AF XY: 0.195

Gnomad AFR exome AF: 0.173

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.308

Gnomad EAS exome AF: 0.218

Gnomad FIN exome AF: 0.162

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.188 AC: 272816 AN: 1451846 Hom.: 26597 Cov.: 28 AF XY: 0.191 AC XY: 137929 AN XY: 722946

African (AFR) AF: 0.169 AC: 5631 AN: 33276

American (AMR) AF: 0.115 AC: 5139 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 7938 AN: 26082

East Asian (EAS) AF: 0.217 AC: 8590 AN: 39640

South Asian (SAS) AF: 0.252 AC: 21657 AN: 86046

European-Finnish (FIN) AF: 0.169 AC: 9028 AN: 53402

Middle Eastern (MID) AF: 0.205 AC: 1182 AN: 5758

European-Non Finnish (NFE) AF: 0.183 AC: 201964 AN: 1102874

Other (OTH) AF: 0.195 AC: 11687 AN: 60058

GnomAD4 genome AF: 0.177 AC: 26913 AN: 152058 Hom.: 2485 Cov.: 32 AF XY: 0.175 AC XY: 13001 AN XY: 74344

African (AFR) AF: 0.169 AC: 7003 AN: 41482

American (AMR) AF: 0.128 AC: 1960 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1039 AN: 3472

East Asian (EAS) AF: 0.207 AC: 1063 AN: 5146

South Asian (SAS) AF: 0.230 AC: 1111 AN: 4826

European-Finnish (FIN) AF: 0.157 AC: 1658 AN: 10578

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12508 AN: 67966

Other (OTH) AF: 0.161 AC: 340 AN: 2110

Alfa AF: 0.196 Hom.: 559

Bravo AF: 0.177

Asia WGS AF: 0.195 AC: 682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Benign	0.82
PhyloP100		1.3
Mutation Taster		=97/3	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: rs2242255; hg19: chr10-75597289; COSMIC: COSV59480692; COSMIC: COSV59480692;