rs2633312

Variant names:

• chr10-73871997-T-A
• rs2633312
• NM_001367534.1:c.160+992A>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+992A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,018 control chromosomes in the GnomAD database, including 17,578 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 0.47 (17578 hom., cov: 31)
• Consequence: CAMK2G NM_001367534.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 8 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=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2G	NM_001367534.1	c.160+992A>T		intron_variant	Intron 2 of 22	ENST00000423381.6	NP_001354463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK2G	ENST00000423381.6	c.160+992A>T		intron_variant	Intron 2 of 22	5	NM_001367534.1	ENSP00000410298.3

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70971 AN: 151900 Hom.: 17579 Cov.: 31

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.467 AC: 70996 AN: 152018 Hom.: 17578 Cov.: 31 AF XY: 0.460 AC XY: 34156 AN XY: 74274

African (AFR) AF: 0.377 AC: 15642 AN: 41476

American (AMR) AF: 0.440 AC: 6717 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1984 AN: 3470

East Asian (EAS) AF: 0.116 AC: 600 AN: 5176

South Asian (SAS) AF: 0.315 AC: 1518 AN: 4816

European-Finnish (FIN) AF: 0.451 AC: 4757 AN: 10546

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 38011 AN: 67946

Other (OTH) AF: 0.529 AC: 1113 AN: 2104

Alfa AF: 0.502 Hom.: 2469

Bravo AF: 0.461

Asia WGS AF: 0.205 AC: 714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.69
PhyloP100		1.4
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: rs2633312; hg19: chr10-75631755;