4-113505588-C-T

Variant names:

• chr4-113505588-C-T
• rs6533690
• NM_001321571.2:c.985-553G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321571.2(CAMK2D):​c.985-553G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 138,876 control chromosomes in the GnomAD database, including 22,431 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 0.60 (22431 hom., cov: 27)
• Consequence: CAMK2D NM_001321571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279
• Publications: 1 publications found

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

ENSG00000308709 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2D	NM_001321571.2	c.985-553G>A		intron_variant	Intron 13 of 20	ENST00000511664.6	NP_001308500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK2D	ENST00000511664.6	c.985-553G>A		intron_variant	Intron 13 of 20	2	NM_001321571.2	ENSP00000425824.1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 82889 AN: 138756 Hom.: 22380 Cov.: 27

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.625

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.592

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.598 AC: 82993 AN: 138876 Hom.: 22431 Cov.: 27 AF XY: 0.593 AC XY: 40010 AN XY: 67466

African (AFR) AF: 0.772 AC: 30857 AN: 39954

American (AMR) AF: 0.572 AC: 7984 AN: 13954

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1786 AN: 3152

East Asian (EAS) AF: 0.382 AC: 1596 AN: 4182

South Asian (SAS) AF: 0.440 AC: 1844 AN: 4188

European-Finnish (FIN) AF: 0.462 AC: 4267 AN: 9228

Middle Eastern (MID) AF: 0.627 AC: 158 AN: 252

European-Non Finnish (NFE) AF: 0.539 AC: 33077 AN: 61316

Other (OTH) AF: 0.587 AC: 1150 AN: 1960

Alfa AF: 0.592 Hom.: 3779

Bravo AF: 0.626

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.22
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6533690; hg19: chr4-114426744;