7-44220086-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001220.5(CAMK2B):c.1977C>T(p.Gly659=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 1,601,746 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (57 hom., cov: 34)
  • Exomes 𝑓: 0.0016 (53 hom.)
• Consequence: CAMK2B NM_001220.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.75

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 7-44220086-G-A is Benign according to our data. Variant chr7-44220086-G-A is described in ClinVar as [Benign]. Clinvar id is 783493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.75 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (2046/152304) while in subpopulation AFR AF= 0.0455 (1892/41560). AF 95% confidence interval is 0.0438. There are 57 homozygotes in gnomad4. There are 943 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High AC in GnomAd at 2042 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMK2B	NM_001220.5	c.1977C>T	p.Gly659=	synonymous_variant	23/24	ENST00000395749.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK2B	ENST00000395749.7	c.1977C>T	p.Gly659=	synonymous_variant	23/24	1	NM_001220.5

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2042 AN: 152186 Hom.: 56 Cov.: 34

Gnomad AFR AF: 0.0456

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00641

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00372 AC: 856 AN: 230216 Hom.: 20 AF XY: 0.00274 AC XY: 344 AN XY: 125652

Gnomad AFR exome AF: 0.0467

Gnomad AMR exome AF: 0.00237

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00194

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000242

Gnomad OTH exome AF: 0.00297

GnomAD4 exome AF: 0.00156 AC: 2255 AN: 1449442 Hom.: 53 Cov.: 32 AF XY: 0.00141 AC XY: 1019 AN XY: 720754

Gnomad4 AFR exome AF: 0.0468

Gnomad4 AMR exome AF: 0.00265

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.00202

Gnomad4 FIN exome AF: 0.0000210

Gnomad4 NFE exome AF: 0.000153

Gnomad4 OTH exome AF: 0.00368

GnomAD4 genome AF: 0.0134 AC: 2046 AN: 152304 Hom.: 57 Cov.: 34 AF XY: 0.0127 AC XY: 943 AN XY: 74458

Gnomad4 AFR AF: 0.0455

Gnomad4 AMR AF: 0.00640

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.00554 Hom.: 7

Bravo AF: 0.0156

Asia WGS AF: 0.00202 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

CAMK2B-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	1.7
Dann	Benign	0.91

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: rs77158048; hg19: chr7-44259685; COSMIC: COSV51662860;