chr4-113531250-A-T

Position:

• chr4-113531250-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001321571.2(CAMK2D):​c.567T>A​(p.Asp189Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAMK2D NM_001321571.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28

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]

CAMK2D (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08474839).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMK2D	NM_001321571.2	c.567T>A	p.Asp189Glu	missense_variant	8/21	ENST00000511664.6	NP_001308500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMK2D	ENST00000511664.6	c.567T>A	p.Asp189Glu	missense_variant	8/21	2	NM_001321571.2	ENSP00000425824.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.87
DEOGEN2	Benign	0.015	.;.;T;T;.;T;.;T;.;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.83	T;T;T;T;T;T;T;T;.;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.085	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.27	N;N;.;N;N;.;N;.;N;N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.89	N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.072
Sift	Benign	0.96	T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T;T;T
Polyphen		0.0	B;.;B;B;B;.;.;.;.;.
Vest4		0.29
MutPred		0.34		Gain of glycosylation at Y191 (P = 0.0099);Gain of glycosylation at Y191 (P = 0.0099);Gain of glycosylation at Y191 (P = 0.0099);Gain of glycosylation at Y191 (P = 0.0099);Gain of glycosylation at Y191 (P = 0.0099);Gain of glycosylation at Y191 (P = 0.0099);Gain of glycosylation at Y191 (P = 0.0099);Gain of glycosylation at Y191 (P = 0.0099);Gain of glycosylation at Y191 (P = 0.0099);Gain of glycosylation at Y191 (P = 0.0099);
MVP		0.30
MPC		1.1
ClinPred		0.37	T
GERP RS		1.2
Varity_R		0.21
gMVP		0.30

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: chr4-114452406;