chr7-44220107-G-A

Variant names:

• chr7-44220107-G-A
• rs1065359
• NM_001220.5:c.1956C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001220.5(CAMK2B):​c.1956C>T​(p.Asn652Asn) 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CAMK2B	NM_001220.5	c.1956C>T	p.Asn652Asn	synonymous_variant	Exon 23 of 24	ENST00000395749.7	NP_001211.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK2B	ENST00000395749.7	c.1956C>T	p.Asn652Asn	synonymous_variant	Exon 23 of 24	1	NM_001220.5	ENSP00000379098.2

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

GnomAD2 exomes AF: 0.406 AC: 97604 AN: 240622 AF XY: 0.411

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 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 AC: 6701 AN: 33424

Gnomad4 AMR exome AF: 0.369 AC: 16319 AN: 44272

Gnomad4 ASJ exome AF: 0.455 AC: 11867 AN: 26056

Gnomad4 EAS exome AF: 0.322 AC: 12738 AN: 39578

Gnomad4 SAS exome AF: 0.439 AC: 37788 AN: 86008

Gnomad4 FIN exome AF: 0.506 AC: 25421 AN: 50230

Gnomad4 NFE exome AF: 0.421 AC: 467369 AN: 1110606

Gnomad4 Remaining exome AF: 0.405 AC: 24385 AN: 60260

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 AC: 0.212934 AN: 0.212934

Gnomad4 AMR AF: 0.357 AC: 0.356807 AN: 0.356807

Gnomad4 ASJ AF: 0.446 AC: 0.445821 AN: 0.445821

Gnomad4 EAS AF: 0.364 AC: 0.363654 AN: 0.363654

Gnomad4 SAS AF: 0.441 AC: 0.44053 AN: 0.44053

Gnomad4 FIN AF: 0.514 AC: 0.513695 AN: 0.513695

Gnomad4 NFE AF: 0.422 AC: 0.422164 AN: 0.422164

Gnomad4 OTH AF: 0.346 AC: 0.346408 AN: 0.346408

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

Mar 30, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Intellectual disability, autosomal dominant 54 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	4.0
DANN	Benign	0.85
Mutation Taster		=99/1	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

Publications

LitVar

Other links and lift over

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