7-44220272-C-G

Variant names:

• chr7-44220272-C-G
• rs1127065
• NM_001220.5:c.1791G>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001220.5(CAMK2B):​c.1791G>C​(p.Pro597Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,612,832 control chromosomes in the GnomAD database, including 360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. P597P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.014 (20 hom., cov: 33)
  • Exomes 𝑓: 0.020 (340 hom.)
• Consequence: CAMK2B NM_001220.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.83
• Publications: 36 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 7-44220272-C-G is Benign according to our data. Variant chr7-44220272-C-G is described in ClinVar as Benign. ClinVar VariationId is 1616494.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.83 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0141 (2142/152108) while in subpopulation SAS AF = 0.0253 (122/4820). AF 95% confidence interval is 0.0217. There are 20 homozygotes in GnomAd4. There are 1054 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2142 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2B	NM_001220.5	c.1791G>C	p.Pro597Pro	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.1791G>C	p.Pro597Pro	synonymous_variant	Exon 23 of 24	1	NM_001220.5	ENSP00000379098.2

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2141 AN: 151992 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.00413

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.0330

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0198

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.0170 AC: 4213 AN: 248552 AF XY: 0.0177

Gnomad AFR exome AF: 0.00336

Gnomad AMR exome AF: 0.00490

Gnomad ASJ exome AF: 0.0126

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.0390

Gnomad NFE exome AF: 0.0192

Gnomad OTH exome AF: 0.0160

GnomAD4 exome AF: 0.0199 AC: 29112 AN: 1460724 Hom.: 340 Cov.: 45 AF XY: 0.0202 AC XY: 14702 AN XY: 726648

African (AFR) AF: 0.00311 AC: 104 AN: 33478

American (AMR) AF: 0.00561 AC: 251 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 368 AN: 26126

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.0270 AC: 2331 AN: 86236

European-Finnish (FIN) AF: 0.0391 AC: 2055 AN: 52518

Middle Eastern (MID) AF: 0.0104 AC: 60 AN: 5766

European-Non Finnish (NFE) AF: 0.0205 AC: 22775 AN: 1111828

Other (OTH) AF: 0.0193 AC: 1165 AN: 60372

GnomAD4 genome AF: 0.0141 AC: 2142 AN: 152108 Hom.: 20 Cov.: 33 AF XY: 0.0142 AC XY: 1054 AN XY: 74332

African (AFR) AF: 0.00412 AC: 171 AN: 41490

American (AMR) AF: 0.00431 AC: 66 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5166

South Asian (SAS) AF: 0.0253 AC: 122 AN: 4820

European-Finnish (FIN) AF: 0.0330 AC: 349 AN: 10588

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0198 AC: 1344 AN: 67954

Other (OTH) AF: 0.0128 AC: 27 AN: 2108

Alfa AF: 0.000790 Hom.: 23538

EpiCase AF: 0.0183

EpiControl AF: 0.0159

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.8
DANN	Benign	0.82
PhyloP100		-3.8
Mutation Taster		=94/6	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: rs1127065; hg19: chr7-44259871;