7-44223857-T-C

Variant names:

• chr7-44223857-T-C
• rs1003573
• NM_001220.5:c.1597+2659A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001220.5(CAMK2B):​c.1597+2659A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 151,902 control chromosomes in the GnomAD database, including 28,210 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 0.61 (28210 hom., cov: 31)
• Consequence: CAMK2B NM_001220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

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.1597+2659A>G		intron	N/A	NP_001211.3
	CAMK2B	NM_001293170.2		c.1226-2956A>G		intron	N/A	NP_001280099.1	Q13554-2
	CAMK2B	NM_172078.3		c.1226-2956A>G		intron	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.1597+2659A>G		intron	N/A	ENSP00000379098.2	Q13554-1
	CAMK2B	ENST00000440254.6	TSL:1	c.1226-2956A>G		intron	N/A	ENSP00000397937.2	Q13554-2
	CAMK2B	ENST00000395747.6	TSL:1	c.1154-2956A>G		intron	N/A	ENSP00000379096.2	Q13554-5

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92471 AN: 151784 Hom.: 28185 Cov.: 31

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.609 AC: 92549 AN: 151902 Hom.: 28210 Cov.: 31 AF XY: 0.613 AC XY: 45542 AN XY: 74236

African (AFR) AF: 0.603 AC: 24965 AN: 41388

American (AMR) AF: 0.660 AC: 10079 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2181 AN: 3466

East Asian (EAS) AF: 0.576 AC: 2968 AN: 5150

South Asian (SAS) AF: 0.633 AC: 3051 AN: 4818

European-Finnish (FIN) AF: 0.625 AC: 6605 AN: 10562

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40834 AN: 67922

Other (OTH) AF: 0.618 AC: 1303 AN: 2110

Alfa AF: 0.606 Hom.: 35564

Bravo AF: 0.611

Asia WGS AF: 0.573 AC: 1995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.98
DANN	Benign	0.58
PhyloP100		-1.7
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: rs1003573; hg19: chr7-44263456;