7-44220089-CGA-ACT

Variant names:

• chr7-44220089-CGA-ACT
• NM_001220.5:c.1972_1974delTCGinsAGT
• CAMK2B p.659

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001220.5(CAMK2B):​c.1972_1974delTCGinsAGT​(p.659) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S658S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CAMK2B NM_001220.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.54
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001220.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2B	NM_001220.5	MANE Select	c.1972_1974delTCGinsAGT	p.659	synonymous	N/A	NP_001211.3
	CAMK2B	NM_001293170.2		c.1600_1602delTCGinsAGT	p.535	synonymous	N/A	NP_001280099.1	Q13554-2
	CAMK2B	NM_172078.3		c.1600_1602delTCGinsAGT	p.535	synonymous	N/A	NP_742075.1	Q13554-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2B	ENST00000395749.7	TSL:1 MANE Select	c.1972_1974delTCGinsAGT	p.659	synonymous	N/A	ENSP00000379098.2	Q13554-1
	CAMK2B	ENST00000440254.6	TSL:1	c.1600_1602delTCGinsAGT	p.535	synonymous	N/A	ENSP00000397937.2	Q13554-2
	CAMK2B	ENST00000395747.6	TSL:1	c.1528_1530delTCGinsAGT	p.511	synonymous	N/A	ENSP00000379096.2	Q13554-5

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-44259688;