chr4-113661737-G-A
Position:
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
NM_001321571.2 missense
Scores
10
6
3
Clinical Significance
Conservation
PhyloP100: 9.22
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 |
---|---|---|---|---|---|---|---|
CAMK2D | NM_001321571.2 | c.196C>T | p.Arg66Cys | missense_variant | 3/21 | ENST00000511664.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAMK2D | ENST00000511664.6 | c.196C>T | p.Arg66Cys | missense_variant | 3/21 | 2 | NM_001321571.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000136 AC: 2AN: 147060Hom.: 0 AF XY: 0.0000260 AC XY: 2AN XY: 76960
GnomAD3 exomes
AF:
AC:
2
AN:
147060
Hom.:
AF XY:
AC XY:
2
AN XY:
76960
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000444 AC: 6AN: 1350228Hom.: 0 Cov.: 23 AF XY: 0.00000600 AC XY: 4AN XY: 666768
GnomAD4 exome
AF:
AC:
6
AN:
1350228
Hom.:
Cov.:
23
AF XY:
AC XY:
4
AN XY:
666768
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ExAC
AF:
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 submitter | clinical testing | Ambry Genetics | May 27, 2022 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;.;T;T;.;T;.;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D;D;.;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;M;M;.;M;.;M;M
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D;D;D;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D;D;D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D;D
Polyphen
B;.;P;B;B;.;.;.;.;.
Vest4
MutPred
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
MPC
2.7
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at