Genetic Variant NM_001220.5:c.1987G>T (chr7-44220076-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001220.5(CAMK2B):c.1987G>T(p.Ala663Ser) variant causes a missense change involving the alteration of a 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.51

Publications

0 publications found

Variant links:

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

CAMK2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29967034).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001220.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CAMK2B	NM_001220.5	MANE Select	c.1987G>T	p.Ala663Ser	missense	Exon 23 of 24	NP_001211.3
CAMK2B	NM_001293170.2		c.1615G>T	p.Ala539Ser	missense	Exon 20 of 21	NP_001280099.1	Q13554-2
CAMK2B	NM_172078.3		c.1615G>T	p.Ala539Ser	missense	Exon 20 of 21	NP_742075.1	Q13554-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CAMK2B	ENST00000395749.7	TSL:1 MANE Select	c.1987G>T	p.Ala663Ser	missense	Exon 23 of 24	ENSP00000379098.2	Q13554-1
CAMK2B	ENST00000440254.6	TSL:1	c.1615G>T	p.Ala539Ser	missense	Exon 20 of 21	ENSP00000397937.2	Q13554-2
CAMK2B	ENST00000395747.6	TSL:1	c.1543G>T	p.Ala515Ser	missense	Exon 19 of 19	ENSP00000379096.2	Q13554-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1442268

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716748

African (AFR)

AF:

0.00

AC:

AN:

33104

American (AMR)

AF:

0.00

AC:

AN:

42962

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25822

East Asian (EAS)

AF:

0.00

AC:

AN:

38840

South Asian (SAS)

AF:

0.00

AC:

AN:

84452

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45912

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105632

Other (OTH)

AF:

0.00

AC:

AN:

59806

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.30

MetaSVM

Uncertain

-0.094

MutationAssessor

Benign

1.3

PhyloP100

7.5

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.4

REVEL

Benign

0.24

Sift

Benign

0.052

Sift4G

Uncertain

0.057

Polyphen

0.15

Vest4

0.45

MutPred

0.13

Gain of glycosylation at A663 (P = 0.0178)

MVP

0.77

MPC

1.2

ClinPred

0.94

GERP RS

4.3

Varity_R

0.15

gMVP

0.46

Mutation Taster

=59/41

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over