rs1554385203

Variant names:

• chr7-44241751-T-A
• rs1554385203
• NM_001220.5:c.852A>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 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
• Publications: 0 publications found

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]

CAMK2B Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 40

  Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina
• intellectual disability, autosomal dominant 54

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-44241751-T-A is Pathogenic according to our data. Variant chr7-44241751-T-A is described in ClinVar as Pathogenic. ClinVar VariationId is 560180.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2B	NM_001220.5	c.852A>T	p.Arg284Ser	missense_variant	Exon 11 of 24	ENST00000395749.7	NP_001211.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK2B	ENST00000395749.7	c.852A>T	p.Arg284Ser	missense_variant	Exon 11 of 24	1	NM_001220.5	ENSP00000379098.2

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

Apr 28, 2022

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

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
PhyloP100		-0.27
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
Mutation Taster		=0/100	disease causing (ClinVar)

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: rs1554385203; hg19: chr7-44281350;