dbSNP rs4834348: CAMK2D:c.985-124C>A (chr4-113505159-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001321571.2(CAMK2D):c.985-124C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 473,122 control chromosomes in the GnomAD database, including 46,515 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 14771 hom., cov: 30)

Exomes 𝑓: 0.43 ( 31744 hom. )

Consequence

CAMK2D
NM_001321571.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.66

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

CAMK2D-related neurodevelopmental disorder and dilated cardiomyopathy
Inheritance: AD Classification: MODERATE Submitted by: G2P
complex neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

CAMK2D links:

ENSG00000308709 (HGNC:):

ENSG00000308709 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2D	NM_001321571.2 link	c.985-124C>A		intron_variant	Intron 13 of 20	ENST00000511664.6	NP_001308500.1	E9PF82

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK2D	ENST00000511664.6 link	c.985-124C>A		intron_variant	Intron 13 of 20	2	NM_001321571.2	ENSP00000425824.1		E9PF82

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65693

AN:

151774

Hom.:

14769

Cov.:

show subpopulations

Gnomad AFR

AF:

0.466

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.474

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.471

Gnomad OTH

AF:

0.464

GnomAD4 exome

AF:

0.430

AC:

138125

AN:

321230

Hom.:

31744

AF XY:

0.432

AC XY:

73522

AN XY:

169994

show subpopulations

African (AFR)

AF:

0.463

AC:

3798

AN:

8206

American (AMR)

AF:

0.323

AC:

3441

AN:

10642

Ashkenazi Jewish (ASJ)

AF:

0.483

AC:

5261

AN:

10888

East Asian (EAS)

AF:

0.119

AC:

2853

AN:

23998

South Asian (SAS)

AF:

0.398

AC:

7195

AN:

18062

European-Finnish (FIN)

AF:

0.363

AC:

8619

AN:

23768

Middle Eastern (MID)

AF:

0.543

AC:

1689

AN:

3110

European-Non Finnish (NFE)

AF:

0.476

AC:

96607

AN:

202958

Other (OTH)

AF:

0.442

AC:

8662

AN:

19598

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

3535

7070

10605

14140

17675

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

508

1016

1524

2032

2540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.433

AC:

65718

AN:

151892

Hom.:

14771

Cov.:

AF XY:

0.421

AC XY:

31241

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.465

AC:

19269

AN:

41400

American (AMR)

AF:

0.362

AC:

5528

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.474

AC:

1644

AN:

3468

East Asian (EAS)

AF:

0.104

AC:

535

AN:

5158

South Asian (SAS)

AF:

0.376

AC:

1812

AN:

4816

European-Finnish (FIN)

AF:

0.339

AC:

3575

AN:

10552

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.471

AC:

31970

AN:

67908

Other (OTH)

AF:

0.459

AC:

970

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1801

3601

5402

7202

9003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

612

1224

1836

2448

3060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.462

Hom.:

8646

Bravo

AF:

0.436

Asia WGS

AF:

0.248

AC:

863

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over