4-113465556-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001321571.2(CAMK2D):āc.1184T>Cā(p.Ile395Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,613,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.000022 ( 0 hom. )
Consequence
CAMK2D
NM_001321571.2 missense
NM_001321571.2 missense
Scores
7
9
3
Clinical Significance
Conservation
PhyloP100: 8.90
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.771
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAMK2D | NM_001321571.2 | c.1184T>C | p.Ile395Thr | missense_variant | 17/21 | ENST00000511664.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAMK2D | ENST00000511664.6 | c.1184T>C | p.Ile395Thr | missense_variant | 17/21 | 2 | NM_001321571.2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152196Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251136Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135728
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GnomAD4 exome AF: 0.0000219 AC: 32AN: 1460832Hom.: 0 Cov.: 28 AF XY: 0.0000275 AC XY: 20AN XY: 726754
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152314Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74472
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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 | Aug 08, 2023 | The c.1082T>C (p.I361T) alteration is located in exon 15 (coding exon 15) of the CAMK2D gene. This alteration results from a T to C substitution at nucleotide position 1082, causing the isoleucine (I) at amino acid position 361 to be replaced by a threonine (T). 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
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;.;T;T;.;T;.;T;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;.;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M;.;M;.;.;.;.;M;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D;D;D;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D;D;.
Polyphen
P;.;P;P;P;.;.;.;.;.;.
Vest4
MVP
MPC
1.2
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at