Variant 4-113537357-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001321571.2(CAMK2D):c.501C>A(p.Asp167Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 1,606,330 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 20 hom. )

Consequence

CAMK2D
NM_001321571.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.50

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 4-113537357-G-T is Benign according to our data. Variant chr4-113537357-G-T is described in ClinVar as [Benign]. Clinvar id is 724773.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMK2D	NM_001321571.2 linkuse as main transcript	c.501C>A	p.Asp167Glu	missense_variant	7/21	ENST00000511664.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK2D	ENST00000511664.6 linkuse as main transcript	c.501C>A	p.Asp167Glu	missense_variant	7/21	2	NM_001321571.2

Frequencies

GnomAD3 genomes

AF:

0.00358

AC:

544

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000918

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0108

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00554

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00462

AC:

1160

AN:

250974

Hom.:

AF XY:

0.00450

AC XY:

611

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.000740

Gnomad AMR exome

AF:

0.000958

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0111

Gnomad NFE exome

AF:

0.00740

Gnomad OTH exome

AF:

0.00523

GnomAD4 exome

AF:

0.00453

AC:

6584

AN:

1454088

Hom.:

Cov.:

AF XY:

0.00450

AC XY:

3257

AN XY:

723938

show subpopulations

Gnomad4 AFR exome

AF:

0.000781

Gnomad4 AMR exome

AF:

0.000940

Gnomad4 ASJ exome

AF:

0.0000767

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0116

Gnomad4 NFE exome

AF:

0.00511

Gnomad4 OTH exome

AF:

0.00406

GnomAD4 genome

AF:

0.00357

AC:

544

AN:

152242

Hom.:

Cov.:

AF XY:

0.00356

AC XY:

265

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000915

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0108

Gnomad4 NFE

AF:

0.00554

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00506

Hom.:

Bravo

AF:

0.00292

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00570

AC:

692

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

Cadd

Benign

Dann

Benign

0.97

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.069

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.80

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

MetaRNN

Benign

0.0088

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.52

N;N;.;N;N;.;N;.;N;N

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.88

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

REVEL

Benign

0.12

Sift

Benign

0.59

T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.49

T;T;T;T;T;T;T;T;T;T

Polyphen

0.0

B;.;B;B;B;.;.;.;.;.

Vest4

0.14

MutPred

0.21

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);

MVP

0.44

MPC

1.1

ClinPred

0.014

GERP RS

5.0

Varity_R

0.16

gMVP

0.067

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.21

Position offset: -16

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over