chr4-113513852-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_001321571.2(CAMK2D):​c.881T>C​(p.Phe294Ser) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

CAMK2D
NM_001321571.2 missense

Scores

10
7
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.26
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.886
PP5
Variant 4-113513852-A-G is Pathogenic according to our data. Variant chr4-113513852-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 1343380.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CAMK2DNM_001321571.2 linkuse as main transcriptc.881T>C p.Phe294Ser missense_variant 11/21 ENST00000511664.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CAMK2DENST00000511664.6 linkuse as main transcriptc.881T>C p.Phe294Ser missense_variant 11/212 NM_001321571.2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
24
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Neurodevelopmental disorder Pathogenic:1
Pathogenic, no assertion criteria providedresearchLaboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de NantesMar 07, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Pathogenic
0.28
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
.;.;T;D;.;T;.;T;.;.;.
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;D;D;D;D;D;D;D;.;D;D
M_CAP
Uncertain
0.24
D
MetaRNN
Pathogenic
0.89
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
0.26
D
MutationAssessor
Uncertain
2.5
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
0.91
D
PROVEAN
Pathogenic
-7.0
D;D;D;D;D;D;D;D;D;D;D
REVEL
Pathogenic
0.68
Sift
Pathogenic
0.0
D;D;D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.0050
D;D;D;D;D;D;D;D;D;D;.
Polyphen
0.94
P;.;B;P;P;.;.;.;.;.;.
Vest4
0.92
MutPred
0.69
Gain of disorder (P = 0.0039);Gain of disorder (P = 0.0039);Gain of disorder (P = 0.0039);Gain of disorder (P = 0.0039);Gain of disorder (P = 0.0039);Gain of disorder (P = 0.0039);Gain of disorder (P = 0.0039);Gain of disorder (P = 0.0039);Gain of disorder (P = 0.0039);Gain of disorder (P = 0.0039);.;
MVP
0.83
MPC
3.1
ClinPred
0.99
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.98
gMVP
0.97

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: chr4-114435008; API