chr7-44241751-T-A

Position:

• chr7-44241751-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP2 PP5

The NM_001220.5(CAMK2B):​c.852A>T​(p.Arg284Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAMK2B NM_001220.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.269

Genes affected

CAMK2B (HGNC:1461): (calcium/calmodulin dependent protein kinase II beta) The product of this gene 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 beta chain. It is possible that distinct isoforms of this chain have different cellular localizations and interact differently with calmodulin. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CAMK2B. . Gene score misZ 4.0707 (greater than the threshold 3.09). Trascript score misZ 3.3558 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 54, intellectual disability, autosomal dominant 40, autosomal dominant non-syndromic intellectual disability.
• PP5: Variant 7-44241751-T-A is Pathogenic according to our data. Variant chr7-44241751-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 560180.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMK2B	NM_001220.5	c.852A>T	p.Arg284Ser	missense_variant	11/24	ENST00000395749.7	NP_001211.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMK2B	ENST00000395749.7	c.852A>T	p.Arg284Ser	missense_variant	11/24	1	NM_001220.5	ENSP00000379098

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Intellectual disability, autosomal dominant 54 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 28, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.73	.;.;D;.;.;.;.;.;.;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.16	N
LIST_S2	Uncertain	0.96	.;.;D;D;D;D;D;D;D;D
M_CAP	Pathogenic	0.40	D
MetaRNN	Uncertain	0.64	D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Pathogenic	2.9	M;M;M;M;M;M;M;M;M;M
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-5.7	D;D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D;D;D;D;D;D;D;T;D;D
Sift4G	Benign	0.085	T;T;D;T;T;T;T;T;T;T
Polyphen		1.0	D;D;D;D;D;P;D;P;D;D
Vest4		0.67
MutPred		0.43		Loss of MoRF binding (P = 0.0399);Loss of MoRF binding (P = 0.0399);Loss of MoRF binding (P = 0.0399);Loss of MoRF binding (P = 0.0399);Loss of MoRF binding (P = 0.0399);Loss of MoRF binding (P = 0.0399);Loss of MoRF binding (P = 0.0399);Loss of MoRF binding (P = 0.0399);Loss of MoRF binding (P = 0.0399);Loss of MoRF binding (P = 0.0399);
MVP		0.74
MPC		2.8
ClinPred		1.0	D
GERP RS		-3.4
Varity_R		0.88
gMVP		0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554385203; hg19: chr7-44281350;