chr10-73869638-G-A

Variant names:

• chr10-73869638-G-A
• rs4746154
• NM_001367534.1:c.160+3351C>T

Variant summary

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

The NM_001367534.1(CAMK2G):​c.160+3351C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,204 control chromosomes in the GnomAD database, including 2,171 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 0.16 (2171 hom., cov: 33)
• Consequence: CAMK2G NM_001367534.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.513
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.24 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.160+3351C>T		intron	N/A	NP_001354463.1
	CAMK2G	NM_001320898.2		c.160+3351C>T		intron	N/A	NP_001307827.1
	CAMK2G	NM_001367544.1		c.160+3351C>T		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.160+3351C>T		intron	N/A	ENSP00000410298.3
	CAMK2G	ENST00000322635.7	TSL:1	c.160+3351C>T		intron	N/A	ENSP00000315599.3
	CAMK2G	ENST00000394762.7	TSL:1	c.-594+3351C>T		intron	N/A	ENSP00000378243.4

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24323 AN: 152086 Hom.: 2171 Cov.: 33

Gnomad AFR AF: 0.0965

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.152

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.160 AC: 24321 AN: 152204 Hom.: 2171 Cov.: 33 AF XY: 0.158 AC XY: 11766 AN XY: 74414

African (AFR) AF: 0.0963 AC: 4001 AN: 41530

American (AMR) AF: 0.120 AC: 1833 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3470

East Asian (EAS) AF: 0.204 AC: 1059 AN: 5188

South Asian (SAS) AF: 0.252 AC: 1213 AN: 4816

European-Finnish (FIN) AF: 0.159 AC: 1684 AN: 10602

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12941 AN: 67996

Other (OTH) AF: 0.150 AC: 317 AN: 2116

Alfa AF: 0.173 Hom.: 431

Bravo AF: 0.156

Asia WGS AF: 0.187 AC: 652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.4
DANN	Benign	0.70
PhyloP100		0.51
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: rs4746154; hg19: chr10-75629396;