7-44220083-C-A

Variant names:

• chr7-44220083-C-A
• rs756806590
• NM_001220.5:c.1980G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001220.5(CAMK2B):​c.1980G>T​(p.Ala660Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A660A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CAMK2B NM_001220.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.19
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 7-44220083-C-A is Benign according to our data. Variant chr7-44220083-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2132314.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.19 with no splicing effect.

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.1980G>T	p.Ala660Ala	synonymous	Exon 23 of 24	NP_001211.3
	CAMK2B	NM_001293170.2		c.1608G>T	p.Ala536Ala	synonymous	Exon 20 of 21	NP_001280099.1	Q13554-2
	CAMK2B	NM_172078.3		c.1608G>T	p.Ala536Ala	synonymous	Exon 20 of 21	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.1980G>T	p.Ala660Ala	synonymous	Exon 23 of 24	ENSP00000379098.2	Q13554-1
	CAMK2B	ENST00000440254.6	TSL:1	c.1608G>T	p.Ala536Ala	synonymous	Exon 20 of 21	ENSP00000397937.2	Q13554-2
	CAMK2B	ENST00000395747.6	TSL:1	c.1536G>T	p.Ala512Ala	synonymous	Exon 19 of 19	ENSP00000379096.2	Q13554-5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446308 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718916

African (AFR) AF: 0.00 AC: 0 AN: 33216

American (AMR) AF: 0.00 AC: 0 AN: 43486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25876

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39090

South Asian (SAS) AF: 0.00 AC: 0 AN: 84854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107276

Other (OTH) AF: 0.00 AC: 0 AN: 59924

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	3.4
DANN	Benign	0.83
PhyloP100		-3.2

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: rs756806590; hg19: chr7-44259682;