10-73815031-G-A

Position:

• chr10-73815031-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001367534.1(CAMK2G):​c.1751C>T​(p.Ala584Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAMK2G NM_001367534.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.52

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32307857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMK2G	NM_001367534.1	c.1751C>T	p.Ala584Val	missense_variant	22/23	ENST00000423381.6	NP_001354463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMK2G	ENST00000423381.6	c.1751C>T	p.Ala584Val	missense_variant	22/23	5	NM_001367534.1	ENSP00000410298.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 20, 2024

The c.1655C>T (p.A552V) alteration is located in exon 20 (coding exon 20) of the CAMK2G gene. This alteration results from a C to T substitution at nucleotide position 1655, causing the alanine (A) at amino acid position 552 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Benign	0.22	.;.;.;.;T;.;.;T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;D;D;D;D;D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.32	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.34	.;.;.;.;N;.;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.6	N;N;.;N;.;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.21	T;T;.;T;.;T;T;T
Sift4G	Benign	0.24	T;T;T;T;T;T;T;T
Polyphen		0.0020	B;B;.;.;B;.;B;.
Vest4		0.68
MutPred		0.18		.;.;.;.;Loss of glycosylation at P553 (P = 0.0425);.;.;.;
MVP		0.69
MPC		1.7
ClinPred		0.86	D
GERP RS		5.4
Varity_R		0.28
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1281325090; hg19: chr10-75574789;