chr4-113661737-G-A

Variant summary

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

The NM_001321571.2(CAMK2D):​c.196C>T​(p.Arg66Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000444 in 1,350,228 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

CAMK2D
NM_001321571.2 missense

Scores

10
6
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.22
Variant links:
Genes affected
CAMK2D (HGNC:1462): (calcium/calmodulin dependent protein kinase II delta) 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 delta chain. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Distinct isoforms of this chain have different expression patterns.[provided by RefSeq, Nov 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CAMK2DNM_001321571.2 linkuse as main transcriptc.196C>T p.Arg66Cys missense_variant 3/21 ENST00000511664.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CAMK2DENST00000511664.6 linkuse as main transcriptc.196C>T p.Arg66Cys missense_variant 3/212 NM_001321571.2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000136
AC:
2
AN:
147060
Hom.:
0
AF XY:
0.0000260
AC XY:
2
AN XY:
76960
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000102
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000444
AC:
6
AN:
1350228
Hom.:
0
Cov.:
23
AF XY:
0.00000600
AC XY:
4
AN XY:
666768
show subpopulations
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:
0.0000275
Gnomad4 FIN exome
AF:
0.0000412
Gnomad4 NFE exome
AF:
0.00000192
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000453
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 27, 2022The c.196C>T (p.R66C) alteration is located in exon 3 (coding exon 3) of the CAMK2D gene. This alteration results from a C to T substitution at nucleotide position 196, causing the arginine (R) at amino acid position 66 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Pathogenic
0.26
CADD
Pathogenic
34
DANN
Uncertain
1.0
DEOGEN2
Benign
0.058
.;.;T;T;.;T;.;T;.;.
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.99
D;D;D;D;D;D;D;D;.;D
M_CAP
Uncertain
0.14
D
MetaRNN
Uncertain
0.61
D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.31
T
MutationAssessor
Uncertain
2.1
M;M;.;M;M;.;M;.;M;M
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.89
D
PROVEAN
Pathogenic
-6.3
D;D;D;D;D;D;D;D;D;D
REVEL
Pathogenic
0.65
Sift
Pathogenic
0.0
D;D;D;D;D;D;D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D;D;D;D;D;D;D
Polyphen
0.081
B;.;P;B;B;.;.;.;.;.
Vest4
0.69
MutPred
0.72
Loss of MoRF binding (P = 0.0051);Loss of MoRF binding (P = 0.0051);Loss of MoRF binding (P = 0.0051);Loss of MoRF binding (P = 0.0051);Loss of MoRF binding (P = 0.0051);Loss of MoRF binding (P = 0.0051);Loss of MoRF binding (P = 0.0051);Loss of MoRF binding (P = 0.0051);Loss of MoRF binding (P = 0.0051);Loss of MoRF binding (P = 0.0051);
MVP
0.79
MPC
2.7
ClinPred
0.86
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.88
gMVP
0.44

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs759589868; hg19: chr4-114582893; API