Variant 4-113609162-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001399863.1(CAMK2D):c.-196G>A variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000000705 in 1,418,012 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: 7.1e-7 ( 0 hom. )

Consequence

CAMK2D
NM_001399863.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.45

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]

CAMK2D links:

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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 rank	MANE	Protein	UniProt
CAMK2D	NM_001321571.2 link	c.265G>A	p.Val89Met	missense_variant	Exon 4 of 21	ENST00000511664.6	NP_001308500.1	E9PF82

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK2D	ENST00000511664.6 link	c.265G>A	p.Val89Met	missense_variant	Exon 4 of 21	2	NM_001321571.2	ENSP00000425824.1		E9PF82

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.05e-7

AC:

AN:

1418012

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

708336

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.33e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.265G>A (p.V89M) alteration is located in exon 4 (coding exon 4) of the CAMK2D gene. This alteration results from a G to A substitution at nucleotide position 265, causing the valine (V) at amino acid position 89 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

.;.;T;T;.;T;.;T;.;.

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.97

D;D;D;D;D;D;D;D;.;D

M_CAP

Uncertain

0.087

MetaRNN

Uncertain

0.62

D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.26

MutationAssessor

Pathogenic

3.2

M;M;.;M;M;.;M;.;M;M

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.7

N;N;N;N;N;N;N;N;N;N

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D

Polyphen

0.94

P;.;D;P;D;.;.;.;.;.

Vest4

0.61

MutPred

0.57

Gain of glycosylation at Y87 (P = 0.0647);Gain of glycosylation at Y87 (P = 0.0647);Gain of glycosylation at Y87 (P = 0.0647);Gain of glycosylation at Y87 (P = 0.0647);Gain of glycosylation at Y87 (P = 0.0647);Gain of glycosylation at Y87 (P = 0.0647);Gain of glycosylation at Y87 (P = 0.0647);Gain of glycosylation at Y87 (P = 0.0647);Gain of glycosylation at Y87 (P = 0.0647);Gain of glycosylation at Y87 (P = 0.0647);

MVP

0.50

MPC

2.4

ClinPred

0.99

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.76

gMVP

0.41

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over