4-113513912-T-G

Position:

• chr4-113513912-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001321571.2(CAMK2D):​c.821A>C​(p.Gln274Pro) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAMK2D NM_001321571.2 missense, splice_region
• Scores: Splicing: ADA: 0.09362
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.94

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-113513912-T-G is Pathogenic according to our data. Variant chr4-113513912-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 1343377.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMK2D	NM_001321571.2	c.821A>C	p.Gln274Pro	missense_variant, splice_region_variant	11/21	ENST00000511664.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK2D	ENST00000511664.6	c.821A>C	p.Gln274Pro	missense_variant, splice_region_variant	11/21	2	NM_001321571.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 21

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Neurodevelopmental disorder Pathogenic:1

Pathogenic, no assertion criteria provided

research

Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes

Mar 07, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	26
DANN	Uncertain	0.99
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.76	T;T;T;T;T;T;T;T;.;T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.68	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.030	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	0.88	D
PROVEAN	Uncertain	-4.2	D;D;D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0050	D;D;D;D;D;D;D;D;D;D;D
Sift4G	Benign	0.15	T;T;T;T;T;T;T;T;T;T;.
Polyphen		0.39	B;.;B;B;P;.;.;.;.;.;.
Vest4		0.76
MutPred		0.37		Loss of MoRF binding (P = 0.0713);Loss of MoRF binding (P = 0.0713);Loss of MoRF binding (P = 0.0713);Loss of MoRF binding (P = 0.0713);Loss of MoRF binding (P = 0.0713);Loss of MoRF binding (P = 0.0713);Loss of MoRF binding (P = 0.0713);Loss of MoRF binding (P = 0.0713);Loss of MoRF binding (P = 0.0713);Loss of MoRF binding (P = 0.0713);.;
MVP		0.86
MPC		2.5
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.90
gMVP		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.094
dbscSNV1_RF	Benign	0.49
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: chr4-114435068;