10-73866615-T-C

Variant names:

• chr10-73866615-T-C
• rs2664283
• NM_001367534.1:c.161-5726A>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.161-5726A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.964 in 152,288 control chromosomes in the GnomAD database, including 70,770 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 0.96 (70770 hom., cov: 32)
• Consequence: CAMK2G NM_001367534.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.984 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2G	NM_001367534.1	c.161-5726A>G		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.161-5726A>G		intron_variant	Intron 2 of 22	5	NM_001367534.1	ENSP00000410298.3

Frequencies

GnomAD3 genomes AF: 0.963 AC: 146615 AN: 152170 Hom.: 70711 Cov.: 32

Gnomad AFR AF: 0.992

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.984

Gnomad ASJ AF: 0.979

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.995

Gnomad FIN AF: 0.884

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.972

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

GnomAD4 genome AF: 0.964 AC: 146733 AN: 152288 Hom.: 70770 Cov.: 32 AF XY: 0.963 AC XY: 71675 AN XY: 74452

African (AFR) AF: 0.992 AC: 41220 AN: 41564

American (AMR) AF: 0.984 AC: 15065 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.979 AC: 3399 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5186

South Asian (SAS) AF: 0.995 AC: 4806 AN: 4828

European-Finnish (FIN) AF: 0.884 AC: 9360 AN: 10590

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.950 AC: 64604 AN: 68020

Other (OTH) AF: 0.973 AC: 2058 AN: 2116

Alfa AF: 0.955 Hom.: 68383

Bravo AF: 0.971

Asia WGS AF: 0.996 AC: 3463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.47
PhyloP100		-0.12
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: rs2664283; hg19: chr10-75626373;