7-44220107-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001220.5(CAMK2B):c.1956C>T(p.Asn652=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,608,392 control chromosomes in the GnomAD database, including 138,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10661 hom., cov: 34)
  • Exomes 𝑓: 0.42 (127646 hom.)
• Consequence: CAMK2B NM_001220.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.41

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 Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 7-44220107-G-A is Benign according to our data. Variant chr7-44220107-G-A is described in ClinVar as [Benign]. Clinvar id is 1192566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMK2B	NM_001220.5	c.1956C>T	p.Asn652=	synonymous_variant	23/24	ENST00000395749.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK2B	ENST00000395749.7	c.1956C>T	p.Asn652=	synonymous_variant	23/24	1	NM_001220.5

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55027 AN: 152078 Hom.: 10656 Cov.: 34

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.341

GnomAD3 exomes AF: 0.406 AC: 97604 AN: 240622 Hom.: 20461 AF XY: 0.411 AC XY: 53892 AN XY: 130988

Gnomad AFR exome AF: 0.203

Gnomad AMR exome AF: 0.374

Gnomad ASJ exome AF: 0.450

Gnomad EAS exome AF: 0.347

Gnomad SAS exome AF: 0.437

Gnomad FIN exome AF: 0.509

Gnomad NFE exome AF: 0.423

Gnomad OTH exome AF: 0.401

GnomAD4 exome AF: 0.415 AC: 604627 AN: 1456196 Hom.: 127646 Cov.: 59 AF XY: 0.416 AC XY: 301151 AN XY: 724342

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.369

Gnomad4 ASJ exome AF: 0.455

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.439

Gnomad4 FIN exome AF: 0.506

Gnomad4 NFE exome AF: 0.421

Gnomad4 OTH exome AF: 0.405

GnomAD4 genome AF: 0.362 AC: 55044 AN: 152196 Hom.: 10661 Cov.: 34 AF XY: 0.368 AC XY: 27413 AN XY: 74400

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.346

Alfa AF: 0.407 Hom.: 3192

Bravo AF: 0.339

Asia WGS AF: 0.387 AC: 1346 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 30, 2020	- -

Intellectual disability, autosomal dominant 54 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	4.0
Dann	Benign	0.85

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: rs1065359; hg19: chr7-44259706; COSMIC: COSV51657811;