7-44220079-C-T

Variant names:

• chr7-44220079-C-T
• NM_001220.5:c.1984G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001220.5(CAMK2B):​c.1984G>A​(p.Val662Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CAMK2B NM_001220.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.24

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20208919).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2B	NM_001220.5	c.1984G>A	p.Val662Met	missense_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.1984G>A	p.Val662Met	missense_variant	Exon 23 of 24	1	NM_001220.5	ENSP00000379098.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1444918 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718170

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 662 of the CAMK2B protein (p.Val662Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CAMK2B-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	.;.;T;.;.;.;.;.;.;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.30	N
LIST_S2	Pathogenic	0.97	.;.;D;D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.20	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	0.69	.;.;N;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.85	N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0030	D;D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.74	P;P;D;.;P;B;B;B;P;P;P
Vest4		0.34
MutPred		0.11		.;.;Loss of catalytic residue at V662 (P = 0.0915);.;.;.;.;.;.;.;.;
MVP		0.77
MPC		1.6
ClinPred		0.62	D
GERP RS		4.3
Varity_R		0.14
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-44259678;